Prior probabilities of clinical hypotheses are not systematically used for clinical trial design yet, due to a concern that poor priors may lead to poor decisions. To address this concern, a conservative approach to Bayesian trial design is illustrated here, requiring that the operational characteristics of the primary trial outcome are stronger than the prior. This approach is complementary to current Bayesian design methods, in that it insures against prior-data conflict by defining a sample size commensurate to a discrete design prior. This approach is ethical, in that it requires designs appropriate to achieving pre-specified levels of clinical equipoise imbalance. Practical examples are discussed, illustrating design of trials with binary or time to event endpoints. Moderate increases in phase II study sample size are shown to deliver strong levels of overall evidence for go/no-go clinical development decisions. Levels of negative evidence provided by group sequential confirmatory designs are found negligible, highlighting the importance of complementing efficacy boundaries with non-binding futility criteria.
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Self-driving software pipelines include components that are learned from a significant number of training examples, yet it remains challenging to evaluate the overall system's safety and generalization performance. Together with scaling up the real-world deployment of autonomous vehicles, it is of critical importance to automatically find simulation scenarios where the driving policies will fail. We propose a method that efficiently generates adversarial simulation scenarios for autonomous driving by solving an optimal control problem that aims to maximally perturb the policy from its nominal trajectory. Given an image-based driving policy, we show that we can inject new objects in a neural rendering representation of the deployment scene, and optimize their texture in order to generate adversarial sensor inputs to the policy. We demonstrate that adversarial scenarios discovered purely in the neural renderer (surrogate scene) can often be successfully transferred to the deployment scene, without further optimization. We demonstrate this transfer occurs both in simulated and real environments, provided the learned surrogate scene is sufficiently close to the deployment scene.
Unsupervised anomaly segmentation aims to detect patterns that are distinct from any patterns processed during training, commonly called abnormal or out-of-distribution patterns, without providing any associated manual segmentations. Since anomalies during deployment can lead to model failure, detecting the anomaly can enhance the reliability of models, which is valuable in high-risk domains like medical imaging. This paper introduces Masked Modality Cycles with Conditional Diffusion (MMCCD), a method that enables segmentation of anomalies across diverse patterns in multimodal MRI. The method is based on two fundamental ideas. First, we propose the use of cyclic modality translation as a mechanism for enabling abnormality detection. Image-translation models learn tissue-specific modality mappings, which are characteristic of tissue physiology. Thus, these learned mappings fail to translate tissues or image patterns that have never been encountered during training, and the error enables their segmentation. Furthermore, we combine image translation with a masked conditional diffusion model, which attempts to `imagine' what tissue exists under a masked area, further exposing unknown patterns as the generative model fails to recreate them. We evaluate our method on a proxy task by training on healthy-looking slices of BraTS2021 multi-modality MRIs and testing on slices with tumors. We show that our method compares favorably to previous unsupervised approaches based on image reconstruction and denoising with autoencoders and diffusion models.
This paper studies inference in randomized controlled trials with multiple treatments, where treatment status is determined according to a "matched tuples" design. Here, by a matched tuples design, we mean an experimental design where units are sampled i.i.d. from the population of interest, grouped into "homogeneous" blocks with cardinality equal to the number of treatments, and finally, within each block, each treatment is assigned exactly once uniformly at random. We first study estimation and inference for matched tuples designs in the general setting where the parameter of interest is a vector of linear contrasts over the collection of average potential outcomes for each treatment. Parameters of this form include standard average treatment effects used to compare one treatment relative to another, but also include parameters which may be of interest in the analysis of factorial designs. We first establish conditions under which a sample analogue estimator is asymptotically normal and construct a consistent estimator of its corresponding asymptotic variance. Combining these results establishes the asymptotic exactness of tests based on these estimators. In contrast, we show that, for two common testing procedures based on t-tests constructed from linear regressions, one test is generally conservative while the other generally invalid. We go on to apply our results to study the asymptotic properties of what we call "fully-blocked" 2^K factorial designs, which are simply matched tuples designs applied to a full factorial experiment. Leveraging our previous results, we establish that our estimator achieves a lower asymptotic variance under the fully-blocked design than that under any stratified factorial design which stratifies the experimental sample into a finite number of "large" strata. A simulation study and empirical application illustrate the practical relevance of our results.
Submodular maximization under various constraints is a fundamental problem studied continuously, in both computer science and operations research, since the late $1970$'s. A central technique in this field is to approximately optimize the multilinear extension of the submodular objective, and then round the solution. The use of this technique requires a solver able to approximately maximize multilinear extensions. Following a long line of work, Buchbinder and Feldman (2019) described such a solver guaranteeing $0.385$-approximation for down-closed constraints, while Oveis Gharan and Vondr\'ak (2011) showed that no solver can guarantee better than $0.478$-approximation. In this paper, we present a solver guaranteeing $0.401$-approximation, which significantly reduces the gap between the best known solver and the inapproximability result. The design and analysis of our solver are based on a novel bound that we prove for DR-submodular functions. This bound improves over a previous bound due to Feldman et al. (2011) that is used by essentially all state-of-the-art results for constrained maximization of general submodular/DR-submodular functions. Hence, we believe that our new bound is likely to find many additional applications in related problems, and to be a key component for further improvement.
To quantify uncertainty, conformal prediction methods are gaining continuously more interest and have already been successfully applied to various domains. However, they are difficult to apply to time series as the autocorrelative structure of time series violates basic assumptions required by conformal prediction. We propose HopCPT, a novel conformal prediction approach for time series that not only copes with temporal structures but leverages them. We show that our approach is theoretically well justified for time series where temporal dependencies are present. In experiments, we demonstrate that our new approach outperforms state-of-the-art conformal prediction methods on multiple real-world time series datasets from four different domains.
The surge in developing deep learning models for diagnosing skin lesions through image analysis is notable, yet their clinical black faces challenges. Current dermatology AI models have limitations: limited number of possible diagnostic outputs, lack of real-world testing on uncommon skin lesions, inability to detect out-of-distribution images, and over-reliance on dermoscopic images. To address these, we present an All-In-One \textbf{H}ierarchical-\textbf{O}ut of Distribution-\textbf{C}linical Triage (HOT) model. For a clinical image, our model generates three outputs: a hierarchical prediction, an alert for out-of-distribution images, and a recommendation for dermoscopy if clinical image alone is insufficient for diagnosis. When the recommendation is pursued, it integrates both clinical and dermoscopic images to deliver final diagnosis. Extensive experiments on a representative cutaneous lesion dataset demonstrate the effectiveness and synergy of each component within our framework. Our versatile model provides valuable decision support for lesion diagnosis and sets a promising precedent for medical AI applications.
Joint modeling is a useful approach to dynamic prediction of clinical outcomes using longitudinally measured predictors. When the outcomes are competing risk events, fitting the conventional shared random effects joint model often involves intensive computation, especially when multiple longitudinal biomarkers are be used as predictors, as is often desired in prediction problems. Motivated by a longitudinal cohort study of chronic kidney disease, this paper proposes a new joint model for the dynamic prediction of end-stage renal disease with the competing risk of death. The model factorizes the likelihood into the distribution of the competing risks data and the distribution of longitudinal data given the competing risks data. The estimation with the EM algorithm is efficient, stable and fast, with a one-dimensional integral in the E-step and convex optimization for most parameters in the M-step, regardless of the number of longitudinal predictors. The model also comes with a consistent albeit less efficient estimation method that can be quickly implemented with standard software, ideal for model building and diagnotics. This model enables the prediction of future longitudinal data trajectories conditional on being at risk at a future time, a practically significant problem that has not been studied in the statistical literature. We study the properties of the proposed method using simulations and a real dataset and compare its performance with the shared random effects joint model.
Understanding causality helps to structure interventions to achieve specific goals and enables predictions under interventions. With the growing importance of learning causal relationships, causal discovery tasks have transitioned from using traditional methods to infer potential causal structures from observational data to the field of pattern recognition involved in deep learning. The rapid accumulation of massive data promotes the emergence of causal search methods with brilliant scalability. Existing summaries of causal discovery methods mainly focus on traditional methods based on constraints, scores and FCMs, there is a lack of perfect sorting and elaboration for deep learning-based methods, also lacking some considers and exploration of causal discovery methods from the perspective of variable paradigms. Therefore, we divide the possible causal discovery tasks into three types according to the variable paradigm and give the definitions of the three tasks respectively, define and instantiate the relevant datasets for each task and the final causal model constructed at the same time, then reviews the main existing causal discovery methods for different tasks. Finally, we propose some roadmaps from different perspectives for the current research gaps in the field of causal discovery and point out future research directions.
Object detection typically assumes that training and test data are drawn from an identical distribution, which, however, does not always hold in practice. Such a distribution mismatch will lead to a significant performance drop. In this work, we aim to improve the cross-domain robustness of object detection. We tackle the domain shift on two levels: 1) the image-level shift, such as image style, illumination, etc, and 2) the instance-level shift, such as object appearance, size, etc. We build our approach based on the recent state-of-the-art Faster R-CNN model, and design two domain adaptation components, on image level and instance level, to reduce the domain discrepancy. The two domain adaptation components are based on H-divergence theory, and are implemented by learning a domain classifier in adversarial training manner. The domain classifiers on different levels are further reinforced with a consistency regularization to learn a domain-invariant region proposal network (RPN) in the Faster R-CNN model. We evaluate our newly proposed approach using multiple datasets including Cityscapes, KITTI, SIM10K, etc. The results demonstrate the effectiveness of our proposed approach for robust object detection in various domain shift scenarios.
Detecting carried objects is one of the requirements for developing systems to reason about activities involving people and objects. We present an approach to detect carried objects from a single video frame with a novel method that incorporates features from multiple scales. Initially, a foreground mask in a video frame is segmented into multi-scale superpixels. Then the human-like regions in the segmented area are identified by matching a set of extracted features from superpixels against learned features in a codebook. A carried object probability map is generated using the complement of the matching probabilities of superpixels to human-like regions and background information. A group of superpixels with high carried object probability and strong edge support is then merged to obtain the shape of the carried object. We applied our method to two challenging datasets, and results show that our method is competitive with or better than the state-of-the-art.
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