Counterfactual Sensitivity and Robustness

Researchers frequently make parametric assumptions about the distribution of unobservables when formulating structural models. Such assumptions are typically motived by computational convenience rather than economic theory and are often untestable. Counterfactuals can be particularly sensitive to such assumptions, threatening the credibility of structural modeling exercises. To address this issue, we leverage insights from the literature on ambiguity and model uncertainty to propose a tractable econometric framework for characterizing the sensitivity of counterfactuals with respect to a researcher's assumptions about the distribution of unobservables in a class of structural models. In particular, we show how to construct the smallest and largest values of the counterfactual as the distribution of unobservables spans nonparametric neighborhoods of the researcher's assumed specification while other `structural' features of the model, e.g. equilibrium conditions, are maintained. Our methods are computationally simple to implement, with the nuisance distribution effectively profiled out via a low-dimensional convex program. Our procedure delivers sharp bounds for the identified set of counterfactuals (i.e. without parametric assumptions about the distribution of unobservables) as the neighborhoods become large. Over small neighborhoods, we relate our procedure to a measure of local sensitivity which is further characterized using an influence function representation. We provide a suitable sampling theory for plug-in estimators and apply our procedure to models of strategic interaction and dynamic discrete choice

Essays on Structural Dynamic Discrete Models

In the dynamic discrete choice model of Rust (1987), any economic variable relevant to decision-making and correlated across time must be observed by the econometrician. This can be an inconvenient restriction. In the first chapter of this thesis, "Hidden Rust Models", I introduce a class of models allowing for unobserved dynamics in a dynamic discrete choice context. Hidden Rust models can be thought of as partially observed classical Rust models. There is an unobserved component to the discrete Markovian state variable. The unobserved random utility shocks (the "epsilons") remain independent and identically distributed across time. This makes the estimation of hidden Rust models fast and convenient. By contrast, the popular alternative models with autoregressive random utility shocks (AR(1) epsilons) is much harder to estimate. The chapter focuses on the practical estimation of hidden Rust models and illustrates their use in a model of dynamic financial incentives inspired by Duflo et al. (2012). A hidden Rust model can be seen as a partially observed Markov chain whose transition matrix is constrained by economic theory. There are two types of constraints: (1) conditional independences and structural zero transition probabilities (2) compatibility with a lower-dimensional utility parameter in accordance with the economic model of decision-making. Many lessons from chapter 1 carry over to any economic model fitting this description. Those structural dynamic discrete models are what brings together the three chapters of this thesis. In the second chapter, "Algebraic models have a generic and stable identification structure", I study the issue of identification for models whose identification equation can be written as a system of polynomial equations, "algebraic models" for short. Structural dynamic discrete models are a foremost example of algebraic models. I show that algebraic models have a generic identification structure and that dynamic algebraic models have a stable identification structure. In the last chapter of this thesis, "Times-series asymptotics for structural dynamic discrete models", I prove that structural dynamic discrete models have good statisical asymptotic properties under a set of assumptions geared at hidden Rust models in particular, and I comment on extensions to more general models

The Ottawa Score Performs Poorly to Identify Cancer Patients at High Risk of Recurrent Venous Thromboembolism: Insights from the TROPIQUE Study and Updated Meta-Analysis

International audienceThe Ottawa score (OS) for predicting the risk of recurrent venous thromboembolism (VTE) in cancer patients with VTE may help to guide anticoagulant treatment decisions that will optimize benefit-risk ratios. However, data on its reliability are conflicting. We applied the OS to all cancer patients with VTE enrolled in the prospective multicenter TROPIQUE study who received low-molecular-weight heparin over a 6-month period. Of 409 patients, 171 (41.8%) had a high-risk OS. The 6-month cumulative incidence of recurrent VTE was 7.8% (95%CI 4.2–14.8) in the high-risk OS group versus 4.8% (95%CI 2.6–8.9) in the low-risk OS group (SHR 1.47; 95%CI 0.24–8.55). The Area Under the Receiver Operating Characteristic curve (AUROC) of the OS in identifying patients who developed recurrent VTE was 0.53 (95%CI 0.38–0.65), and its accuracy was 57.9%. Among individual variables included in the OS, only prior VTE was significantly associated with the 6-month risk of recurrent VTE (SHR 4.39; 95% CI 1.13–17.04). When pooling data from all studies evaluating this score for predicting VTE recurrence in cancer patients (7 studies, 3413 patients), the OS estimated pooled AUROC was 0.59 (95%CI 0.56–0.62), and its accuracy was 55.7%. The present findings do not support the use of the OS to assess the risk of recurrent VTE in cancer patients

Understanding the Pathophysiology of Intracranial Aneurysm: The ICAN Project

International audienceBACKGROUND: Understanding the pathophysiologic mechanism of intracranial aneurysm (IA) formation is a prerequisite to assess the potential risk of rupture. Nowadays, there are neither reliable biomarkers nor diagnostic tools to predict the formation or the evolution of IA. Increasing evidence suggests a genetic component of IA but genetics studies have failed to identify genetic variation causally related to IA.OBJECTIVE: To develop diagnostic and predictive tools for the risk of IA formation and rupture.METHODS: The French ICAN project is a noninterventional nationwide and multicentric research program. Each typical IA of bifurcation will be included. For familial forms, further IA screening will be applied among first-degree relatives. By accurate phenotype description with high-throughput genetic screening, we aim to identify new genes involved in IA. These potential genetic markers will be tested in large groups of patients. Any relevant pathway identified will be further explored in a large cohort of sporadic carriers of IA, which will be well documented with clinical, biological, and imaging data.EXPECTED OUTCOMES: Discovering genetic risk factors, better understanding the pathophysiology, and identifying molecular mechanisms responsible for IA formation will be essential bases for the development of biomarkers and identification of therapeutic targets.DISCUSSION: Our protocol has many assets. A nationwide recruitment allows for the inclusion of large pedigrees with familial forms of IA. It will combine accurate phenotyping and comprehensive imaging with high-throughput genetic screening. Last, it will enable exploiting metadata to explore new pathophysiological pathways of interest by crossing clinical, genetic, biological, and imaging information

Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm

International audienceIntracranial aneurysms (IAs) are acquired cerebrovascular abnormalities characterized by localized dilation and wall thinning in intracranial arteries, possibly leading to subarachnoid hemorrhage and severe outcome in case of rupture. Here, we identified one rare nonsense variant (c.1378A>T) in the last exon of ANGPTL6 (Angiopoietin-Like 6)—which encodes a circulating pro-angiogenic factor mainly secreted from the liver—shared by the four tested affected members of a large pedigree with multiple IA-affected case subjects. We showed a 50% reduction of ANGPTL6 serum concentration in individuals heterozygous for the c.1378A>T allele (p.Lys460Ter) compared to relatives homozygous for the normal allele, probably due to the non-secretion of the truncated protein produced by the c.1378A>T transcripts. Sequencing ANGPTL6 in a series of 94 additional index case subjects with familial IA identified three other rare coding variants in five case subjects. Overall, we detected a significant enrichment (p = 0.023) in rare coding variants within this gene among the 95 index case subjects with familial IA, compared to a reference population of 404 individuals with French ancestry. Among the 6 recruited families, 12 out of 13 (92%) individuals carrying IA also carry such variants in ANGPTL6, versus 15 out of 41 (37%) unaffected ones. We observed a higher rate of individuals with a history of high blood pressure among affected versus healthy individuals carrying ANGPTL6 variants, suggesting that ANGPTL6 could trigger cerebrovascular lesions when combined with other risk factors such as hypertension. Altogether, our results indicate that rare coding variants in ANGPTL6 are causally related to familial forms of IA