Heterogeneous Values Research Articles

Using Genomic Heterogeneity to Inform Therapeutic Decisions for Metastatic Colorectal Cancer: An Application of the Value of Heterogeneity Framework.

Mutations in KRAS and NRAS are predictive of poor response to cetuximab and panitumumab, two anti-epidermal growth factor receptor (EGFR) monoclonal antibodies used in metastatic colorectal cancer (mCRC). Our objective was to explore the value of using KRAS and NRAS mutation status to inform third-line anti-EGFR therapy for mCRC using the value of heterogeneity (VOH) framework. We used administrative data to identify mCRC patients who were potentially eligible for third-line therapy in 2006-2019 in British Columbia (BC), Canada. We compared three alternative stratification policies in place during the study period: the unstratified policy where anti-EGFR therapy was not offered (2006-2009), stratification by KRAS mutation (2009-2016), and stratification by KRAS+NRAS mutation (2016-2019). We used inverse-probability-of-treatment weighting to balance covariates across the three groups. Cost and survival time were calculated using a 3-year time horizon and adjusted for censoring, with bootstrapping to characterize uncertainty. Mean net monetary benefit (NMB) was calculated at a range of threshold values. The VOH of using KRAS and NRAS mutation status to inform treatment selection was calculated as the change in NMB with increasing stratification, under current (static VOH) or perfect (dynamic VOH) information. We included 2664 patients in the analysis. At a willingness-to-pay of CA$100,000/ life-year gained (LYG), stratification on KRAS mutation status provided a static VOH of CA$1565 per patient; further stratification on KRAS+NRAS provided additional static VOH of CA$594. The static VOH exceeded the marginal cost of genomic testing under both policies. Stratification of anti-EGFR therapy by KRAS and NRAS mutation status can provide additional value at a threshold of CA$100,000/LYG. There is diminishing marginal value and increasing marginal costs as the policy becomes more stratified. The VOH framework can illustrate the value of subgroup-specific decisions in a comprehensive way, to better inform targeted treatment policies.

Bottleneck model with heterogeneous information

This paper studies the effects of heterogeneous information on traffic equilibria and the resulting travel costs (both individual and social) when commuters make departure time choices to cross an unreliable bottleneck link. Increasing adoption and improved predictive abilities of Traveler Information Systems (TIS) enable commuters to plan their trips; however, there are inherent heterogeneities in information access and TIS accuracies. Our work addresses the open problem posed in Arnott et al. (1991) about the need to consider asymmetrically informed commuters in the bottleneck model of traffic congestion. We consider a Bayesian game with two heterogeneous commuter populations: one population is privately informed of the realized network state while the other only knows the public information about the distribution of states. We characterize the equilibrium of the game, in which each population chooses a departure rate function over time to minimize its expected cost based on its private belief about the state and the behavior of the other population. We provide a full equilibrium characterization for the complete range of values of link reliability, incident probability, and information penetration. The populations’ equilibrium strategies can broadly be categorized into two distinct regimes. Specifically, when information penetration is above a certain threshold, the populations’ equilibrium strategies are non-unique, and the relative Value of Information (VoI) is 0, i.e. the two populations face the same cost. On the other hand, when information penetration is below the threshold, equilibrium is unique, and VoI is positive and decreasing in information penetration. Importantly, we find that the lowest social cost is always achieved when a non-zero fraction of commuters are uninformed. The more unreliable the link, the higher the information penetration that achieves this minimum. We define the Value of Heterogeneity (VoH) as the difference between the minimum social cost and the cost under complete information penetration, and find that it can be significant under practically relevant conditions.

OP68 Methods For The Economic Evaluation Of Precision Medicine

Introduction:Methods that accommodate heterogeneity in outcomes are not widely used in economic evaluation. With the growth of precision medicine (PM), where choice of treatment is informed by the molecular characteristics of the patient or disease, we expect to see greater heterogeneity in effectiveness and cost of interventions. Our objective was to compare analytical frameworks for valuing heterogeneity in economic evaluation, and consider their strengths and weaknesses for applications in PM.Methods:We conducted a literature review to identify papers that proposed an analytical framework for economic evaluation of a health intervention, and that placed a value on heterogeneous effects. We compared the frameworks considering the purpose of the analysis, including where in the product lifecycle the framework could be used, the types of PM interventions where the framework could be applied, and its ability to address methodological challenges of evaluating PM.Results:Five analytical frameworks were identified: covariate adjustment methods, value of stratification, value of heterogeneity (VoH), expected value of individualized care (EVIC), and loss with respect to efficient diffusion (LED) metrics. Each framework addresses a slightly different research question, and is suited to different settings and interventions. With the exception of covariate adjustment, all focus on maximizing net benefit within certain constraints and quantify the opportunity cost of ignoring heterogeneity. Only VoH considers the relationship between heterogeneity and uncertainty, and no framework explicitly includes the cost or uncertainty associated with identifying subgroups.Conclusions:The ability to value heterogeneity is a critical component of economic evaluations of PM. The choice of an appropriate analytical framework will help strengthen the quality of economic evidence available to support health technology assessment of PM technologies, informing PM adoption decisions, and supporting efficient allocation of health care resources.

An Algorithm of Image Heterogeneity with Contrast-Enhanced Ultrasound in Differential Diagnosis of Solid Thyroid Nodules

Enhancement heterogeneity on contrast-enhanced ultrasonography (CEUS) is used to differentiate between benign and malignant thyroid nodules. In this study, we used an algorithm to quantify enhancement heterogeneity of solid thyroid nodules on CEUS. The heterogeneity value (HV) is calculated as standard deviation/mean intensity × 100 (using Adobe Photoshop). The heterogeneity ratio (HR) is calculated as the ratio of the HV of the nodule to that of the surrounding parenchyma. Three phases—ascending, peak and descending phases—were studied. HV values at ascending (HVa) and peak (HVp) phases were significantly higher in malignant nodules than in benign nodules (95.57 ± 43.87 vs. 73.06 ± 44.04, p = 0.009, and 32.53 ± 10.73 vs. 26.44 ± 8.25, p = 0.002, respectively). HRa, HRp and HRd were significantly higher in malignant nodules than in benign nodules (1.93 ± 1.03 vs. 1.00 ± 0.47, p = 0.000, 1.43 ± 0.51 vs. 1.09 ± 0.28, p = 0.000, and 1.33 ± 0.40 vs. 1.08 ± 0.33, p = 0.001, respectively). HRa achieved optimal diagnostic performance on receiver operating characteristic curve analysis. The algorithm used for assessment of image heterogeneity on CEUS examination may be a useful adjunct to conventional ultrasound for differential diagnosis of solid thyroid nodules.

Heterogeneous ventilation and perfusion: a sensitive indicator of lung impairment in nonsmoking coal miners

Twenty life-long nonsmoking West Virginia coal-miners participated in a study to amplify the role of focal irregularities on regional ventilation (V) and perfusion (Q) and to develop an improved method for the early detection of coal-workers' pneumoconiosis. Their mean age was 59.3 yr and they averaged 35.2 years' exposure to coal dust. Conventional pulmonary function tests were supplemented by measurement of V, Q and lung volume (V), using radioactive Kr-81m, Tc-99m MAA and Xe-127, respectively, to determine regional abnormalities in lung function. A computer analysis of the regional distributions of V/V, Q/V and V/Q was performed, and their topographical distributions and indices of heterogeneity (HI) computed. V/V and Q/V were significantly reduced in the lower third, and increased in the upper two-thirds of the miners' lungs; V/Q was reduced in the upper half. The miners' V/V and Q/V were more heterogeneous (p less than 0.001) than that of eleven age-matched controls, with mean ventilation HI values of 0.190 +/- 0.027 and 0.133 +/- 0.011, respectively, and mean perfusion HI values of 0.206 +/- 0.022 and 0.164 +/- 0.041, respectively. P(A-a)O2 correlated positively (r = 0.72; p less than 0.001) with ventilation HI. Gas exchange was the most significant functional measurement, being abnormal in 19/20 subjects. In contrast, conventional spirometric measurements were within the predicted normal limits in all but four miners.