A Blueprint for Multi-use Disease Modeling in Health Economics: Results from Two Expert-Panel Consultations.

BACKGROUND: The current use of health economic decision models in HTA is mostly confined to single use cases, which may be inefficient and result in little consistency over different treatment comparisons, and consequently inconsistent health policy decisions, for the same disorder. Multi-use disease models (MUDMs) (other terms: generic models, whole disease models, disease models) may offer a solution. However, much is uncertain about their definition and application. The current research aimed to develop a blueprint for the application of MUDMs. METHODS: We elicited expert opinion using a two-round modified Delphi process. The panel consisted of experts and stakeholders in health economic modelling from various professional backgrounds. The first questionnaire concerned definition, terminology, potential applications, issues and recommendations for MUDMs and was based on an exploratory scoping review. In the second round, the panel members were asked to reconsider their input, based on feedback regarding first-round results, and to score issues and recommendations for priority. Finally, adding input from external advisors and policy makers in a structured way, an overview of issues and challenges was developed during two team consensus meetings. RESULTS: In total, 54 respondents contributed to the panel results. The term 'multi-use disease models' was proposed and agreed upon, and a definition was provided. The panel prioritized 10 potential applications (with comparing alternative policies and supporting resource allocation decisions as the top 2), while 20 issues (with model transparency and stakeholders' roles as the top 2) were identified as challenges. Opinions on potential features concerning operationalization of multi-use models were given, with 11 of these subsequently receiving high priority scores (regular updates and revalidation after updates were the top 2). CONCLUSIONS: MUDMs would improve on current decision support regarding cost-effectiveness information. Given feasibility challenges, this would be most relevant for diseases with multiple treatments, large burden of disease and requiring more complex models. The current overview offers policy makers a starting point to organize the development, use, and maintenance of MUDMs and to support choices concerning which diseases and policy decisions they will be helpful for.

Hospitalisation costs and health related quality of life in delirious patients: a scoping review.

INTRODUCTION: Delirium is a common condition of a global disturbance of cognition, triggered by underlying diseases. The objective of this study is to review the current evidence in the literature on direct healthcare costs and health-related quality of life (HRQOL) associated with delirium. METHODS: A systematic search was conducted in PubMed and Embase for relevant studies published between January 1, 2010 and November 4, 2021. Studies for inclusion reported estimates on healthcare costs or HRQOL, adjusted for relevant confounding factors. RESULTS: Fourteen studies on healthcare costs and eleven studies on HRQOL were included. Delirium resulted in (adjusted) increased costs ranging from $1,532 to $22,269 depending on included cost categories, the country and the type of hospital department. Increased length of stay for delirious patients ranged from 2.5 days to 10.4 days and had the largest contribution to overall, direct incremental costs. Heterogeneity was observed in HRQOL outcomes. CONCLUSION: The analysis indicates that the presence of a delirium episode may lead to increased costs of hospitalisation. Changes in HRQOL due to delirium are not well demonstrated and more research is needed to determine the effect of delirium on HRQOL.

Accuracy of approximations to recover incompletely reported logistic regression models depended on other available information.

OBJECTIVE: To provide approximations to recover the full regression equation across different scenarios of incompletely reported prediction models that were developed from binary logistic regression. STUDY DESIGN AND SETTING: In a case study, we considered four common scenarios and illustrated their corresponding approximations: (A) Missing: the intercept, Available: the regression coefficients of predictors, overall frequency of the outcome and descriptive statistics of the predictors; (B) Missing: regression coefficients and the intercept, Available: a simplified score; (C) Missing: regression coefficients and the intercept, Available: a nomogram; (D) Missing: regression coefficients and the intercept, Available: a web calculator. RESULTS: In the scenario A, a simplified approach based on the predicted probability corresponding to the average linear predictor was inaccurate. An approximation based on the overall outcome frequency and an approximation of the linear predictor distribution was more accurate, however, the appropriateness of the underlying assumptions cannot be verified in practice. In the scenario B, the recovered equation was inaccurate due to rounding and categorization of risk scores. In the scenarios C and D, the full regression equation could be recovered with minimal error. CONCLUSION: The accuracy of the approximations in recovering the regression equation varied depending on the available information.

Cerebrospinal fluid leakage costs after craniotomy and health economic assessment of incidence reduction from a hospital perspective in the Netherlands.

OBJECTIVES: We aim to quantify the cost difference between patients with incisional cerebrospinal fluid (iCSF) leakage and those without after intradural cranial surgery. Second, the potential cost savings per patient when a decrease in iCSF leakage rate would be achieved with and without added costs for preventative measures of various price and efficacy are modelled. DESIGN: Health economic assessment from a hospital perspective based on a retrospective cohort study. SETTING: Dutch tertiary referral centre. PARTICIPANTS: We included 616 consecutive patients who underwent intradural cranial surgery between 1 September 2017 and 1 September 2018. Patients undergoing burr hole surgery or transsphenoidal surgery, or who died within 1 month after surgery or were lost to follow-up were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes of the cost analysis include a detailed breakdown of mean costs per patient for patients with postoperative iCSF leakage and patients without, and the mean cost difference. For the scenario analyses the outcomes are the potential cost savings per 1000 patients when a decrease in iCSF leakage would be achieved. RESULTS: Mean cost difference between patients with and without iCSF leakage was €9665 (95%CI, €5125 to €14 205). The main cost driver was hospital stay with a difference of 8.5 days. A 25% incidence reduction would result in a mean cost saving of -€94 039 (95% CI, -€218 258 to -€7077) per 1000 patients. A maximum cost reduction of -€653 025 (95% CI, -€1 204 243 to -€169 120) per 1000 patients could be achieved if iCSF leakage would be reduced with 75% in all patients, with 72 cases of iCSF leakage avoided. CONCLUSIONS: Postoperative iCSF leakage after intradural cranial surgery increases healthcare costs significantly and substantially. From a health economic perspective preventative measures to avoid iCSF leakage should be pursued.

Advanced image-supported lead placement in cardiac resynchronisation therapy: protocol for the multicentre, randomised controlled ADVISE trial and early economic evaluation.

INTRODUCTION: Achieving optimal placement of the left ventricular (LV) lead in cardiac resynchronisation therapy (CRT) is a prerequisite in order to achieve maximum clinical benefit, and is likely to help avoid non-response. Pacing outside scar tissue and targeting late activated segments may improve outcome. The present study will be the first randomised controlled trial to compare the efficacy of real-time image-guided LV lead delivery to conventional CRT implantation. In addition, to estimate the cost-effectiveness of targeted lead implantation, an early decision analytic model was developed, and described here. METHODS AND ANALYSIS: A multicentre, interventional, randomised, controlled trial will be conducted in a total of 130 patients with a class I or IIa indication for CRT implantation. Patients will be stratified to ischaemic heart failure aetiology and 1:1 randomised to either empirical lead placement or live image-guided lead placement. Ultimate lead location and echocardiographic assessment will be performed by core laboratories, blinded to treatment allocation and patient information. Late gadolinium enhancement cardiac magnetic resonance imaging (CMR) and CINE-CMR with feature-tracking postprocessing software will be used to semi-automatically determine myocardial scar and late mechanical activation. The subsequent treatment file with optimal LV-lead positions will be fused with the fluoroscopy, resulting in live target-visualisation during the procedure. The primary endpoint is the difference in percentage of successfully targeted LV-lead location. Secondary endpoints are relative percentage reduction in indexed LV end-systolic volume, a hierarchical clinical endpoint, and quality of life. The early analytic model was developed using a Markov-model, consisting of seven mutually exclusive health states. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Research Ethics Committee Utrecht (NL73416.041.20). All participants are required to provide written informed consent. Results will be submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05053568; Trial NL8666.

Continuation of Anti-TNF in Patients With Ulcerative Colitis in Remission Is Not Cost-effective Compared With Treatment Withdrawal: A Markov Model.

BACKGROUND AND AIMS: Anti-tumour necrosis factor alpha [anti-TNF] treatment accounts for 31% of health care expenditures associated with ulcerative colitis [UC]. Withdrawal of anti-TNF in patients with UC in remission may decrease side effects and infections, while promoting cost containment. Approximately 36% of patients relapse within 12-24 months of anti-TNF withdrawal, but reintroduction of treatment is successful in 80% of patients. We aimed to evaluate the cost-effectiveness of continuation versus withdrawal of anti-TNF in patients with UC in remission. METHODS: We developed a Markov model comparing cost-effectiveness of anti-TNF continuation versus withdrawal, from a health care provider perspective. Transition probabilities were calculated from literature, or estimated by an expert panel of 11 gastroenterologists. Deterministic and probabilistic sensitivity analyses were performed to account for assumptions and uncertainty. The cost-effectiveness threshold was set at an incremental cost-effectiveness ratio of €80,000 per quality-adjusted life-year [QALY]. RESULTS: At 5 years, anti-TNF withdrawal was less costly [-€10,781 per patient], but also slightly less effective [-0.04 QALY per patient] than continued treatment. Continuation of anti-TNF compared with withdrawal costs €300,390/QALY, exceeding the cost-effectiveness threshold. Continued therapy would become cost-effective if the relapse rate following anti-TNF withdrawal was ≥43% higher, or if adalimumab or infliximab [biosimilar] prices fell below €87/40 mg and €66/100 mg, respectively. CONCLUSIONS: Continuation of anti-TNF in UC patients in remission is not cost-effective compared with withdrawal. A stop-and-reintroduction strategy is cost-saving but is slightly less effective than continued therapy. This strategy could be improved by identifying patients at increased risk of relapse.

MRI-guided pulmonary vein isolation for atrial fibrillation: what is good enough? An early health technology assessment.

Next to anticoagulation, pulmonary vein isolation (PVI) is the most important interventional procedure in the treatment of atrial fibrillation (AF). Despite widespread clinical application of this therapy, patients often require multiple procedures to reach clinical success. In contrast to conventional imaging modalities, MRI allows direct visualisation of the ablation lesion. Therefore, the use of real-time MRI to guide cardiac electrophysiology procedures may increase clinical effectiveness. An essential aspect, from a decision-making point of view, is the effect on costs and the potential cost-effectiveness of new technologies. Generally, health technology assessment (HTA) studies are performed when innovations are close to clinical application. However, early stage HTA can inform users, researchers and funders about the ultimate clinical and economic potential of a future innovation. Ultimately, this can guide funding allocation. In this study, we performed an early HTA evaluate MRI-guided PVIs. Methods: We performed an economic evaluation using a decision tree with a time-horizon of 1 year. We calculated the clinical effectiveness (defined as the proportion of patients that is long-term free of AF after a single procedure) required for MRI-guided PVI to be cost-effective compared with conventional treatment. Results: Depending on the cost-effectiveness threshold (willingness to pay for one additional quality-of-life adjusted life year (QALY), interventional MRI (iMRI) guidance for PVI can be cost-effective if clinical effectiveness is 69.8% (at €80 000/QALY) and 77.1% (at €20 000/QALY), compared with 64% for fluoroscopy-guided procedures. Conclusion: Using an early HTA, we established a clinical effectiveness threshold for interventional MRI-guided PVIs that can inform a clinical implementation strategy. If crucial technologies are developed, it seems plausible that iMRI-guided PVIs will be able to reach this threshold.