COVID-19 outbreak has rapidly evolved into a global pandemic. The impact of COVID-19 on patient journeys in oncology represents a new risk to interpretation of trial results and its broad applicability for future clinical practice. We identify key intercurrent events that may occur due to COVID-19 in oncology clinical trials with a focus on time-to-event endpoints and discuss considerations pertaining to the other estimand attributes introduced in the ICH E9 addendum. We propose strategies to handle COVID-19 related intercurrent events, depending on their relationship with malignancy and treatment and the interpretability of data after them. We argue that the clinical trial objective from a world without COVID-19 pandemic remains valid. The estimand framework provides a common language to discuss the impact of COVID-19 in a structured and transparent manner. This demonstrates that the applicability of the framework may even go beyond what it was initially intended for.
Many Stated Preference studies conducted in developing countries provide a low willingness to pay (WTP) for a wide range of goods and services. However, recent studies in these countries indicate that this may partly be a result of the choice of payment vehicle, not the preference for the good. Thus, low WTP may not indicate a low welfare effect for public projects in developing countries. We argue that in a setting where 1) there is imperfect substitutability between money and other measures of wealth (e.g. labor), and 2) institutions are perceived to be corrupt, including payment vehicles that are currently available to the individual and less pron to corruption may be needed to obtain valid welfare estimates. Otherwise, we risk underestimating the welfare benefit of projects. We demonstrate this through a rural household contingent valuation (CV) survey designed to elicit the value of access to reliable irrigation water in Ethiopia. Of the total average annual WTP for access to reliable irrigation service, cash contribution comprises only 24.41 %. The implication is that socially desirable projects might be rejected based on cost-benefit analysis as a result of welfare gain underestimation due to mismatch of payment vehicles choice in valuation study.
We develop a concept of weak identification in linear IV models in which the number of instruments can grow at the same rate or slower than the sample size. We propose a jackknifed version of the classical weak identification-robust Anderson-Rubin (AR) test statistic. Large-sample inference based on the jackknifed AR is valid under heteroscedasticity and weak identification. The feasible version of this statistic uses a novel variance estimator. The test has uniformly correct size and good power properties. We also develop a pre-test for weak identification that is related to the size property of a Wald test based on the Jackknife Instrumental Variable Estimator (JIVE). This new pre-test is valid under heteroscedasticity and with many instruments.
The existing theory of penalized quantile regression for longitudinal data has focused primarily on point estimation. In this work, we investigate statistical inference. We propose a wild residual bootstrap procedure and show that it is asymptotically valid for approximating the distribution of the penalized estimator. The model puts no restrictions on individual effects, and the estimator achieves consistency by letting the shrinkage decay in importance asymptotically. The new method is easy to implement and simulation studies show that it has accurate small sample behavior in comparison with existing procedures. Finally, we illustrate the new approach using U.S. Census data to estimate a model that includes more than eighty thousand parameters.
We derive and asymptotically analyze mass-action models for disease spread that include transient pair formation and dissociation. Populations of unpaired susceptibles and infecteds are distinguished from the population of three types of pairs of individuals; both susceptible, one susceptible and one infected, and both infected. Disease transmission can occur only within a pair consisting of one susceptible individual and one infected individual. By considering the fast pair formation and fast pair dissociation limits, we use a perturbation expansion to formally derive a uniformly valid approximation for the dynamics of the total infected and susceptible populations. Under different parameter regimes, we derive uniformly valid effective equations for the total infected population and compare their results to those of the full mass-action model. Our results are derived from the fundamental mass-action system without implicitly imposing transmission mechanisms such as that used in frequency-dependent models. They provide a new formulation for effective pairing models and are compared with previous models.
An economic model of crime is used to explore the consistent estimation of a simultaneous linear equation without recourse to instrumental variables. A maximum-likelihood procedure (NISE) is introduced, and its results are compared to ordinary least squares and two-stage least squares. The paper is motivated by previous research on the crime model and by the well-known practical problem that valid instruments are frequently unavailable.
Studying the conformations involved in the dimerization of cadherins is highly relevant to understand the development of tissue and its failure, which is associated with tumors and metastases. Experimental techniques, like X-ray crystallography, can usually report only the most stable conformations, missing minority states that could nonetheless be important for the recognition mechanism. Computer simulations could be a valid complement to the experimental approach. However, standard all-atom protein models in explicit solvent are computationally too demanding to search thoroughly the conformational space of multiple chains composed of several hundreds of amino acids. To reach this goal, we resorted to a coarse-grained model in implicit solvent. The standard problem with this kind of models is to find a realistic potential to describe their interactions. We used coevolutionary information from cadherin alignments, corrected by a statistical potential, to build an interaction potential which is agnostic of the experimental conformations of the protein. Using this model, we explored the conformational space of multi-chain systems and validated the results comparing with experimental data. We identified dimeric conformations that are sequence-specific and that can be useful to rationalize the mechanism of recognition between cadherins.
Systemic liquidity risk, defined by the IMF as "the risk of simultaneous liquidity difficulties at multiple financial institutions", is a key topic in macroprudential policy and financial stress analysis. Specialized models to simulate funding liquidity risk and contagion are available but they require not only banks' bilateral exposures data but also balance sheet data with sufficient granularity, which are hardly available. Alternatively, risk analyses on interbank networks have been done via centrality measures of the underlying graph capturing the most interconnected and hence more prone to risk spreading banks. In this paper, we propose a model which relies on an epidemic model which simulate a contagion on the interbank market using the funding liquidity shortage mechanism as contagion process. The model is enriched with country and bank risk features which take into account the heterogeneity of the interbank market. The proposed model is particularly useful when full set of data necessary to run specialized models is not available. Since the interbank network is not fully available, an economic driven reconstruction method is also proposed to retrieve the interbank network by constraining the standard reconstruction methodology to real financial indicators. We show that the contagion model is able to reproduce systemic liquidity risk across different years and countries. This result suggests that the proposed model can be successfully used as a valid alternative to more complex ones.
We study model-free learning methods for the output-feedback Linear Quadratic (LQ) control problem in finite-horizon subject to subspace constraints on the control policy. Subspace constraints naturally arise in the field of distributed control and present a significant challenge in the sense that standard model-based optimization and learning leads to intractable numerical programs in general. Building upon recent results in zeroth-order optimization, we establish model-free sample-complexity bounds for the class of distributed LQ problems where a local gradient dominance constant exists on any sublevel set of the cost function. %which admit a local gradient dominance constant valid on the sublevel set of the cost function. We prove that a fundamental class of distributed control problems - commonly referred to as Quadratically Invariant (QI) problems - as well as others possess this property. To the best of our knowledge, our result is the first sample-complexity bound guarantee on learning globally optimal distributed output-feedback control policies.
For large-scale Internet of Things (IoT), backscatter communication is a promising technology to reduce power consumption and simplify deployment. However, backscatter communication lacks stability, along with limited communication range within a few meters. Due to the limited computation ability of backscatter tags, it is burdensome to effectively adapt the bitrate for the time-varying channel. Thus, backscatter tags are failed to fully utilize the optimal transmission rate. In this paper, we design a system named COOK with self-reliant bitrate adaptation in backscatter communication. Channel symmetry allows backscatter tags to adjust bitrate depending on the received signal strength of the excitation source (ES) without feedback. In addition, the chirp spreading signal is exploited as the ES signal to enable backscatter tags to work under noise floor. Our modulation approach is denoted as Chirp-OOK since the tags reflect the chirp signal by employing the on-off keying modulation. It allows that receiver can decode under the noise floor and the bitrate varies flexibly as the communication range changes. We have implemented the prototype system based on the universal software radio peripheral (USRP) platform. Extensive experiment results demonstrate the effectiveness of the proposed system. Our system provides valid communication distance up to $27m$, which is 7 times as compared with normal backscatter system. The system significantly increases the backscatter communication stability, by supporting bitrate adaptation ranges from 0.33kbps to 1.2Mbps, and guaranteeing the bit error rate (BER) is below 1%.
Vegetation patterns are a characteristic feature of semi-arid regions. On hillsides these patterns occur as stripes running parallel to the contours. The Klausmeier model, a coupled reaction-advection-diffusion system, is a deliberately simple model describing the phenomenon. In this paper, we replace the diffusion term describing plant dispersal by a more realistic nonlocal convolution integral to account for the possibility of long-range dispersal of seeds. Our analysis focuses on the rainfall level at which there is a transition between uniform vegetation and pattern formation. We obtain results, valid to leading order in the large parameter comparing the rate of water flow downhill to the rate of plant dispersal, for a negative exponential dispersal kernel. Our results indicate that both a wider dispersal of seeds and an increase in dispersal rate inhibit the formation of patterns. Assuming an evolutionary trade-off between these two quantities, mathematically motivated by the limiting behaviour of the convolution term, allows us to make comparisons to existing results for the original reaction-advection-diffusion system. These comparisons show that the nonlocal model always predicts a larger parameter region supporting pattern formation. We then numerically extend the results to other dispersal kernels, showing that the tendency to form patterns depends on the type of decay of the kernel.
Canay (2011)'s two-step estimator of quantile panel data models, due to its simple intuition and low computational cost, has been widely used in empirical studies in recent years. In this paper, we revisit the estimator of Canay (2011) and point out that in his asymptotic analysis the bias of his estimator due to the estimation of the fixed effects is mistakenly omitted, and that such omission will lead to invalid inference on the coefficients. To solve this problem, we propose a similar easy-to-implement estimator based on smoothed quantile regressions. The asymptotic distribution of the new estimator is established and the analytical expression of its asymptotic bias is derived. Based on these results, we show how to make asymptotically valid inference based on both analytical and split-panel jackknife bias corrections. Finally, finite sample simulations are used to support our theoretical analysis and to illustrate the importance of bias correction in quantile regressions for panel data.
Quantile Factor Models (QFM) represent a new class of factor models for high-dimensional panel data. Unlike Approximate Factor Models (AFM), where only location-shifting factors can be extracted, QFM also allow to recover unobserved factors shifting other relevant parts of the distributions of observed variables. A quantile regression approach, labeled Quantile Factor Analysis (QFA), is proposed to consistently estimate all the quantile-dependent factors and loadings. Their asymptotic distribution is then derived using a kernel-smoothed version of the QFA estimators. Two consistent model selection criteria, based on information criteria and rank minimization, are developed to determine the number of factors at each quantile. Moreover, in contrast to the conditions required for the use of Principal Components Analysis in AFM, QFA estimation remains valid even when the idiosyncratic errors have heavy-tailed distributions. Three empirical applications (regarding macroeconomic, climate and finance panel data) provide evidence that extra factors shifting the quantiles other than the means could be relevant in practice.
Solving nonlinear model predictive control problems in real time is still an important challenge despite of recent advances in computing hardware, optimization algorithms and tailored implementations. This challenge is even greater when uncertainty is present due to disturbances, unknown parameters or measurement and estimation errors. To enable the application of advanced control schemes to fast systems and on low-cost embedded hardware, we propose to approximate a robust nonlinear model controller using deep learning and to verify its quality using probabilistic validation techniques. We propose a probabilistic validation technique based on finite families, combined with the idea of generalized maximum and constraint backoff to enable statistically valid conclusions related to general performance indicators. The potential of the proposed approach is demonstrated with simulation results of an uncertain nonlinear system.
Optimal power flow (OPF) is one of the most important optimization problems in the energy industry. In its simplest form, OPF attempts to find the optimal power that the generators within the grid have to produce to satisfy a given demand. Optimality is measured with respect to the cost that each generator incurs in producing this power. The OPF problem is non-convex due to the sinusoidal nature of electrical generation and thus is difficult to solve. Using small angle approximations leads to a convex problem known as DC OPF, but this approximation is no longer valid when power grids are heavily loaded. Many approximate solutions have been since put forward, but these do not scale to large power networks. In this paper, we propose using graph neural networks (which are localized, scalable parametrizations of network data) trained under the imitation learning framework to approximate a given optimal solution. While the optimal solution is costly, it is only required to be computed for network states in the training set. During test time, the GNN adequately learns how to compute the OPF solution. Numerical experiments are run on the IEEE-30 and IEEE-118 test cases.
This paper develops a uniformly valid and asymptotically nonconservative test based on projection for a class of shape restrictions. The key insight we exploit is that these restrictions form convex cones, a simple and yet elegant structure that has been barely harnessed in the literature. Based on a monotonicity property afforded by such a geometric structure, we construct a bootstrap procedure that, unlike many studies in nonstandard settings, dispenses with estimation of local parameter spaces, and the critical values are obtained in a way as simple as computing the test statistic. Moreover, by appealing to strong approximations, our framework accommodates nonparametric regression models as well as distributional/density-related and structural settings. Since the test entails a tuning parameter (due to the nonstandard nature of the problem), we propose a data-driven choice and prove its validity. Monte Carlo simulations confirm that our test works well.
How much should you receive in a week to be indifferent to \$ 100 in six months? Note that the indifference requires a rule to ensure the similarity between early and late payments. Assuming that rational individuals have low accuracy, then the following rule is valid: if the amounts to be paid are much less than the personal wealth, then the $q$-exponential discounting guarantees indifference in several periods. Thus, the discounting can be interpolated between hyperbolic and exponential functions due to the low accuracy to distinguish time averages when the payments have low impact on personal wealth. Therefore, there are physical conditions that allow the hyperbolic discounting regardless psycho-behavioral assumption.
We show that moment inequalities in a wide variety of economic applications have a particular linear conditional structure. We use this structure to construct uniformly valid confidence sets that remain computationally tractable even in settings with nuisance parameters. We first introduce least favorable critical values which deliver non-conservative tests if all moments are binding. Next, we introduce a novel conditional inference approach which ensures a strong form of insensitivity to slack moments. Our recommended approach is a hybrid technique which combines desirable aspects of the least favorable and conditional methods. The hybrid approach performs well in simulations calibrated to Wollmann (2018), with favorable power and computational time comparisons relative to existing alternatives.
We propose a robust method for constructing conditionally valid prediction intervals based on models for conditional distributions such as quantile and distribution regression. Our approach can be applied to important prediction problems including cross-sectional prediction, k-step-ahead forecasts, synthetic controls and counterfactual prediction, and individual treatment effects prediction. Our method exploits the probability integral transform and relies on permuting estimated ranks. Unlike regression residuals, ranks are independent of the predictors, allowing us to construct conditionally valid prediction intervals under heteroskedasticity. We establish approximate conditional validity under consistent estimation and provide approximate unconditional validity under model misspecification, overfitting, and with time series data. We also propose a simple "shape" adjustment of our baseline method that yields optimal prediction intervals.
We study preferences estimated from finite choice experiments and provide sufficient conditions for convergence to a unique underlying "true" preference. Our conditions are weak, and therefore valid in a wide range of economic environments. We develop applications to expected utility theory, choice over consumption bundles, menu choice and intertemporal consumption. Our framework unifies the revealed preference tradition with models that allow for errors.