Mix and match. A simulation study on the impact of mixed-Treatment comparison methods on health-economic outcomes

Background Decision-Analytic cost-effectiveness (CE) models combine many parameters, often obtained after meta-Analysis. Aim We compared different methods of mixed-Treatment comparison (MTC) to combine transition and event probabilities derived from several trials, especially with respect to health-economic (HE) outcomes like (quality adjusted) life years and costs. Methods Trials were drawn from a simulated reference population, comparing two of four fictitious interventions. The goal was to estimate the CE between two of these. The amount of heterogeneity between trials was varied in scenarios. Parameter estimates were combined using direct comparison, MTC methods proposed by Song and Puhan, and Bayesian generalized linear fixed effects (GLMFE) and random effects models (GLMRE). Parameters were entered into a Markov model. Parameters and HE outcomes were compare

Self-report versus care provider registration of healthcare utilization: impact on cost and cost-utility

OBJECTIVES: This study aims to compare the impact of two different sources of resource use, self-report versus care provider registrations, on cost and cost utility. METHODS: Data were gathered for a cost-effectiveness study performed alongside a 2-year randomized controlled trial evaluating the effect of an INTERdisciplinary COMmunity-based management program (INTERCOM) for patients with chronic obstructive pulmonary disease (COPD). The program was offered by physiotherapists, dieticians and respiratory nurses. During the 2-year period, patients reported all resource use in a cost booklet. In addition, data on hospital admissions and outpatient visits, visits to the physiotherapist, dietician or respiratory nurse, diet nutrition, and outpatient medication were obtained from administrative records. The cost per quality-adjusted life-year (QALY) was calculated in two ways, using data from the cost booklet or registrations. RESULTS: In total, 175 patients were included in the study. Agreement between self-report and registrations was almost perfect for hospitalizations (rho = 0.93) and physiotherapist visits (rho = 0.86), but above 0.55, moderate, for all other types of care. The total cost difference between the registrations and the cost booklet was 464 euros with the highest difference for hospitalizations 386 euro. Based on the cost booklet the cost difference between the treatment group and usual care was 2,444 euros (95 percent confidence interval [CI], -819 to 5,950), which resulted in a cost-utility of 29,100 euro/QALY. For the registrations, the results were 2,498 euros (95 percent CI, -88 to 6,084) and 29,390 euro/QALY, respectively. CONCLUSIONS: This study showed that the use of self-reported data or data from registrations effected within-group costs, but not between-group costs or the cost utility

Short- and long-term efficacy of a community-based COPD management programme in less advanced COPD: a randomised controlled trial

BACKGROUND: The effectiveness of pulmonary rehabilitation in advanced COPD is well established, but few data are available in less advanced disease. METHODS: In a 2 year randomised controlled trial, 199 patients with an average moderate airflow obstruction but impaired exercise capacity (mean (SD) forced expiratory volume in 1 s (FEV(1)) 60 (16)%, peak work load (Wmax) <70%) were randomised to the INTERdisciplinary COMmunity-based COPD management programme (INTERCOM) or usual care. Intervention consisted of 4 months multidisciplinary rehabilitation followed by a 20-month maintenance phase. Outcomes (4, 12, 24 months): health-related quality of life (St George's Respiratory Questionnaire (SGRQ)), exacerbation frequency, MRC dyspnoea score, cycle endurance time (CET), 6-minute walking distance (6MWD), skeletal muscle strength and patients' and caregivers' perceived effectiveness. RESULTS: Between-group comparison after 4 months revealed the following mean (SE) significant differences in favour of INTERCOM: SGRQ total score 4.06 (1.39), p = 0.004; activity and impact subscores, p<0.01; MRC score 0.33 (0.13), p = 0.01; Wmax 6.0 (2.3) Watt, p = 0.02; CET 221 (104) s, p = 0.04; 6MWD 13 (6) m, p = 0.02; hand grip force 4.3 (1.5) lb, p<0.01; and fat-free mass index 0.34 (0.13) kg/m(2), p = 0.01. Between-group differences over 2 years were as follows: SGRQ 2.60 (1.3), p = 0.04; MRC score 0.21 (0.10), p = 0.048; CET 253 (104) s, p = 0.0156; 6MWD 18 (8) m, p = 0.0155. Exacerbation frequency was not different (RR 1.29 (95% CI 0.89 to 1.87)). Patients' and caregivers' perceived effectiveness significantly favoured the INTERCOM programme (p<0.01). CONCLUSIONS: This study shows that a mu

Exploring the Impact of Adding a Respiratory Dimension to the EQ-5D-5L.

Objectives. To evaluate the impact of adding a respiratory dimension (a bolt-on dimension) to the EQ-5D-5L health state valuations. Methods. Based on extensive regression and principal component analyses, 2 respiratory bolt-on candidates were formulated: R1, limitations in physical activities due to shortness of breath, and R2, breathing problems. Valuation interviews for the selected bol

A five-year model to assess the early cost-effectiveness of new diagnostic tests in the early diagnosis of rheumatoid arthritis

__Background:__ There is a lack of information about the sensitivity, specificity and costs new diagnostic tests should have to improve early diagnosis of rheumatoid arthritis (RA). Our objective was to explore the early cost-effectiveness of various new diagnostic test strategies in the workup of patients with inflammatory arthritis (IA) at risk of having RA. __Methods:__ A decision tree followed by a patient-level state transition model, using data from published literature, cohorts and trials, was used to evaluate diagnostic test strategies. Alternative tests were assessed as add-on to or replacement of the ACR/EULAR 2010 RA classification criteria for all patients and for intermediate-risk patients. Tests included B-cell gene expression (sensitivity 0.60, specificity 0.90, costs €150), MRI (sensitivity 0.90, specificity 0.60, costs €756), IL-6 serum level (sensitivity 0.70, specificity 0.53, costs €50) and genetic assay (sensitivity 0.40, specificity 0.85, costs €750). Patients with IA at risk of RA were followed for 5 years using a societal perspective. Guideline treatment was assumed using tight controlled treatment based on DAS28; if patients had a DAS28 >3.2 at 12 months or later patients could be eligible for starting biological drugs. The outcome was expressed in incremental cost-effectiveness ratios (€2014 per quality-adjusted life year (QALY) gained) and headroom. __Results:__ The B-cell test was the least expensive strategy when used as an add-on and as replacement in intermediate-risk patients, making it the dominant strategy, as it has better health outcomes and lower costs. As add-on for all patients, the B-cell test was also the most cost-effective test strategy. When using a willingness-to-pay threshold of €20,000 per QALY gained, the IL-6 and MRI

Estimating the Prognostic Value of the NTRK Fusion Biomarker for Comparative Effectiveness Research in The Netherlands

Objectives: We evaluated the prognostic value of the neurotrophic tyrosine receptor kinase (NTRK) gene fusions by comparing the survival of patients with NTRK+ tumours with patients without NTRK+ tumours. Methods: We used genomic and clinical registry data from the Center for Personalized Cancer Treatment (CPCT-02) study containing a cohort of cancer patients who were treated in Dutch clinical practice between 2012 and 2020. We performed a propensity score matching analysis, where NTRK+ patients were matched to NTRK− patients in a 1:4 ratio. We subsequently analysed the survival of the matched sample of NTRK+ and NTRK− patients using the Kaplan–Meier method and Cox regression, and performed an analysis of credibility to evaluate the plausibility of our result. Results:Among 3556 patients from the CPCT-02 study with known tumour location, 24 NTRK+ patients were identified. NTRK+ patients were distributed across nine different tumour types: bone/soft tissue, breast, colorectal, head and neck, lung, pancreas, prostate, skin and urinary tract. NTRK fusions involving the NTRK3 gene (46%) and NTRK1 gene (33%) were most common. The survival analysis rendered a hazard ratio (HR) of 1.44 (95% CI 0.81–2.55) for NTRK+ patients. Using the point estimates of three prior studies on the prognostic value of NTRK fusions, our finding that the HR is &gt; 1 was deemed plausible. Conclusions: NTRK+ patients may have an increased risk of death compared with NTRK− patients. When using historic control data to assess the comparative effectiveness of TRK inhibitors, the prognostic value of the NTRK fusion biomarker should therefore be accounted for.</p

Systemic impairment in relation to disease burden in patients with moderate COPD eligible for a lifestyle program. Findings from the INTERCOM trial

Carel R van Wetering1, Floortje E van Nooten2, Stijn J M Mol3, Martine Hoogendoorn2, Maureen P M H Rutten-van M&amp;ouml;lken2, Annemie M Schols41Department of Physiotherapy, M&amp;aacute;xima Medical Centre, Veldhoven, The Netherlands; 2Institute for Medical Technology Assessment, Erasmus Medical Centre, Rotterdam, The Netherlands; 3Department of Respiratory Medicine, M&amp;aacute;xima Medical Centre, Veldhoven, The Netherlands; 4Department of Respiratory Medicine, Maastricht University, Maastricht, The NetherlandsIntroduction: In contrast with the frequency distribution of chronic obstructive pulmonary disease (COPD) stages in the population, in which the majority of the patients is classified as GOLD 2, much less information is available on the prevalence and implications of systemic manifestations in less severe patients relative to GOLD 3 and 4.Aim: To characterize local and systemic impairment in relation to disease burden in a group of GOLD 2 COPD patients (n = 127, forced expiratory volume in one second (SD): 67 (11)% pred) that were eligible for the Interdisciplinary Community-based COPD management (INTERCOM) trial.Methods: Patients were included for this lifestyle program based on a peak exercise capacity (Wmax) &amp;lt;70% of predicted. Metabolic and ventilatory response to incremental cycle ergometry, 6 minute walking distance (6MWD), constant work rate test (CWR), lung function, maximal inspiratory pressure (Pimax), quadriceps force (QF), quadriceps average power (QP) (isokinetic dynamometry), handgrip force (HGF) and body composition were measured. Quality of life (QoL) was assessed by the St. George&amp;rsquo;s Respiratory Questionnaire (SGRQ) and dyspnea by the modified Medical Research Council (MRC) dyspnea scale. Exacerbations and COPD-associated hospital admissions in 12 months prior to the start of the study were recorded. Burden of disease was defined in terms of exercise capacity, QoL, hospitalization, and exacerbation frequency. GOLD 2 patients were compared with reference values and with GOLD 3 patients who were also included in the trial.Results: HGF (77.7 (18.8) % pred) and Pimax (67.1 (22.5)% pred) were impaired in GOLD 2, while QF (93.5 (22.5)% pred) was only modestly decreased. Depletion of FFM was present in 15% of weight stable GOLD 2 patients while only 2% had experienced recent involuntary weight loss. In contrast to Wmax, submaximal exercise capacity, muscle function, and body composition were not significantly different between GOLD 2 and 3 subgroups. Body mass index and fat-free mass index were significantly lower in smokers compared to ex-smokers. In multivariate analysis, QF and diffusing capacity (DLco) were independently associated with Wmax and 6 MWD in GOLD 2 while only 6 MWD was identified as an independent determinant of health-related QoL. HGF was an independent predictor of hospitalization.Conclusions: This study shows that also in patients with moderate COPD, eligible for a lifestyle program based on a decreased exercise capacity, systemic impairment is an important determinant of disease burden and that smoking affects body composition.Keywords: COPD, systemic impairment, lifestyle, pulmonary rehabilitatio

How to Address Uncertainty in Health Economic Discrete-Event Simulation Models

__Background__. Evaluation of personalized treatment options requires health economic models that include multiple patient characteristics. Patient-level discrete-event simulation (DES) models are deemed appropriate because of their ability to simulate a variety of characteristics and treatment pathways. However, DES models are scarce in the literature, and details about their methods are often missing. __Methods__. We describe 4 challenges associated with modeling heterogeneity and structural, stochastic, and parameter uncertainty that can be encountered during the development of DES models. We explain why these are important and how to correctly implement them. To illustrate the impact of the modeling choices discussed, we use (results of) a model for chronic obstructive pulmonary disease (COPD) as a case study. __Results__. The results from the case study showed that, under a correct implementation of the uncertainty in the model, a hypothetical intervention can be deemed as cost-effective. The consequences of incorrect modeling uncertainty included an increase in the incremental cost-effectiveness ratio ranging from 50% to almost a factor of 14, an extended life expectancy of approximately 1.4 years, and an enormously increased uncertainty around the model outcomes. Thus, modeling uncertainty incorrectly can have substantial implications for decision making. __Conclusions__. This article provides guidance on the implementation of uncertainty in DES models and improves the transparency of reporting uncertainty methods. The COPD case study illustrates the issues described in the article and helps understanding them better. The model R code shows how the uncertainty was implemented. For readers not familiar with R, the model’s pseudo-code can be used to understand how the model works. By doing this, we can help other developers, who are likely to face similar challenges to those described here

The disease burden of multimorbidity and its interaction with educational level

INTRODUCTION: Policies to adequately respond to the rise in multimorbidity have top-priority. To understand the actual burden of multimorbidity,