The ICH E9(R1) addendum (2019) proposed principal stratification (PS) as one of five strategies for dealing with intercurrent events. Therefore, understanding the strengths, limitations, and assumptions of PS is important for the broad community of clinical trialists. Many approaches have been developed under the general framework of PS in different areas of research, including experimental and observational studies. These diverse applications have utilized a diverse set of tools and assumptions. Thus, need exists to present these approaches in a unifying manner. The goal of this tutorial is threefold. First, we provide a coherent and unifying description of PS. Second, we emphasize that estimation of effects within PS relies on strong assumptions and we thoroughly examine the consequences of these assumptions to understand in which situations certain assumptions are reasonable. Finally, we provide an overview of a variety of key methods for PS analysis and use a real clinical trial example to illustrate them. Examples of code for implementation of some of these approaches are given in supplemental materials.
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The present study is an extension of the work done in [16] and [10], where a two-level Parareal method with averaging was examined. The method proposed in this paper is a multi-level Parareal method with arbitrarily many levels, which is not restricted to the two-level case. We give an asymptotic error estimate which reduces to the two-level estimate for the case when only two levels are considered. Introducing more than two levels has important consequences for the averaging procedure, as we choose separate averaging windows for each of the different levels, which is an additional new feature of the present study. The different averaging windows make the proposed method especially appropriate for multi-scale problems, because we can introduce a level for each intrinsic scale of the problem and adapt the averaging procedure such that we reproduce the behavior of the model on the particular scale resolved by the level.
The paper traces the development of the use of martingale methods in survival analysis from the mid 1970's to the early 1990's. This development was initiated by Aalen's Berkeley PhD-thesis in 1975, progressed through the work on estimation of Markov transition probabilities, non-parametric tests and Cox's regression model in the late 1970's and early 1980's, and it was consolidated in the early 1990's with the publication of the monographs by Fleming and Harrington (1991) and Andersen, Borgan, Gill and Keiding (1993). The development was made possible by an unusually fast technology transfer of pure mathematical concepts, primarily from French probability, into practical biostatistical methodology, and we attempt to outline some of the personal relationships that helped this happen. We also point out that survival analysis was ready for this development since the martingale ideas inherent in the deep understanding of temporal development so intrinsic to the French theory of processes were already quite close to the surface in survival analysis.
Explainable artificial intelligence (XAI) is essential for enabling clinical users to get informed decision support from AI and comply with evidence-based medical practice. Applying XAI in clinical settings requires proper evaluation criteria to ensure the explanation technique is both technically sound and clinically useful, but specific support is lacking to achieve this goal. To bridge the research gap, we propose the Clinical XAI Guidelines that consist of five criteria a clinical XAI needs to be optimized for. The guidelines recommend choosing an explanation form based on Guideline 1 (G1) Understandability and G2 Clinical relevance. For the chosen explanation form, its specific XAI technique should be optimized for G3 Truthfulness, G4 Informative plausibility, and G5 Computational efficiency. Following the guidelines, we conducted a systematic evaluation on a novel problem of multi-modal medical image explanation with two clinical tasks, and proposed new evaluation metrics accordingly. Sixteen commonly-used heatmap XAI techniques were evaluated and found to be insufficient for clinical use due to their failure in G3 and G4. Our evaluation demonstrated the use of Clinical XAI Guidelines to support the design and evaluation of clinically viable XAI.
Autonomous Micro Aerial Vehicles are deployed for a variety tasks including surveillance and monitoring. Perching and staring allow the vehicle to monitor targets without flying, saving battery power and increasing the overall mission time without the need to frequently replace batteries. This paper addresses the Active Visual Perching (AVP) control problem to autonomously perch on inclined surfaces up to $90^\circ$. Our approach generates dynamically feasible trajectories to navigate and perch on a desired target location, while taking into account actuator and Field of View (FoV) constraints. By replanning in mid-flight, we take advantage of more accurate target localization increasing the perching maneuver's robustness to target localization or control errors. We leverage the Karush-Kuhn-Tucker (KKT) conditions to identify the compatibility between planning objectives and the visual sensing constraint during the planned maneuver. Furthermore, we experimentally identify the corresponding boundary conditions that maximizes the spatio-temporal target visibility during the perching maneuver. The proposed approach works on-board in real-time with significant computational constraints relying exclusively on cameras and an Inertial Measurement Unit (IMU). Experimental results validate the proposed approach and shows the higher success rate as well as increased target interception precision and accuracy with respect to a one-shot planning approach, while still retaining aggressive capabilities with flight envelopes that include large excursions from the hover position on inclined surfaces up to 90$^\circ$, angular speeds up to 750~deg/s, and accelerations up to 10~m/s$^2$.
In human computer interaction (HCI), it is common to evaluate the value of HCI designs, techniques, devices, and systems in terms of their benefit to users. It is less common to discuss the benefit of HCI to computers. Every HCI task allows a computer to receive some data from the user. In many situations, the data received by the computer embodies human knowledge and intelligence in handling complex problems, and/or some critical information without which the computer cannot proceed. In this paper, we present an information-theoretic framework for quantifying the knowledge received by the computer from its users via HCI. We apply information-theoretic measures to some common HCI tasks as well as HCI tasks in complex data intelligence processes. We formalize the methods for estimating such quantities analytically and measuring them empirically. Using theoretical reasoning, we can confirm the significant but often undervalued role of HCI in data intelligence workflows.
The need for data privacy and security -- enforced through increasingly strict data protection regulations -- renders the use of healthcare data for machine learning difficult. In particular, the transfer of data between different hospitals is often not permissible and thus cross-site pooling of data not an option. The Personal Health Train (PHT) paradigm proposed within the GO-FAIR initiative implements an 'algorithm to the data' paradigm that ensures that distributed data can be accessed for analysis without transferring any sensitive data. We present PHT-meDIC, a productively deployed open-source implementation of the PHT concept. Containerization allows us to easily deploy even complex data analysis pipelines (e.g, genomics, image analysis) across multiple sites in a secure and scalable manner. We discuss the underlying technological concepts, security models, and governance processes. The implementation has been successfully applied to distributed analyses of large-scale data, including applications of deep neural networks to medical image data.
Black-box machine learning models are now routinely used in high-risk settings, like medical diagnostics, which demand uncertainty quantification to avoid consequential model failures. Conformal prediction is a user-friendly paradigm for creating statistically rigorous uncertainty sets/intervals for the predictions of such models. Critically, the sets are valid in a distribution-free sense: they possess explicit, non-asymptotic guarantees even without distributional assumptions or model assumptions. One can use conformal prediction with any pre-trained model, such as a neural network, to produce sets that are guaranteed to contain the ground truth with a user-specified probability, such as 90%. It is easy-to-understand, easy-to-use, and general, applying naturally to problems arising in the fields of computer vision, natural language processing, deep reinforcement learning, and so on. This hands-on introduction is aimed to provide the reader a working understanding of conformal prediction and related distribution-free uncertainty quantification techniques with one self-contained document. We lead the reader through practical theory for and examples of conformal prediction and describe its extensions to complex machine learning tasks involving structured outputs, distribution shift, time-series, outliers, models that abstain, and more. Throughout, there are many explanatory illustrations, examples, and code samples in Python. With each code sample comes a Jupyter notebook implementing the method on a real-data example; the notebooks can be accessed and easily run using our codebase.
Since deep neural networks were developed, they have made huge contributions to everyday lives. Machine learning provides more rational advice than humans are capable of in almost every aspect of daily life. However, despite this achievement, the design and training of neural networks are still challenging and unpredictable procedures. To lower the technical thresholds for common users, automated hyper-parameter optimization (HPO) has become a popular topic in both academic and industrial areas. This paper provides a review of the most essential topics on HPO. The first section introduces the key hyper-parameters related to model training and structure, and discusses their importance and methods to define the value range. Then, the research focuses on major optimization algorithms and their applicability, covering their efficiency and accuracy especially for deep learning networks. This study next reviews major services and toolkits for HPO, comparing their support for state-of-the-art searching algorithms, feasibility with major deep learning frameworks, and extensibility for new modules designed by users. The paper concludes with problems that exist when HPO is applied to deep learning, a comparison between optimization algorithms, and prominent approaches for model evaluation with limited computational resources.
Causal inference is a critical research topic across many domains, such as statistics, computer science, education, public policy and economics, for decades. Nowadays, estimating causal effect from observational data has become an appealing research direction owing to the large amount of available data and low budget requirement, compared with randomized controlled trials. Embraced with the rapidly developed machine learning area, various causal effect estimation methods for observational data have sprung up. In this survey, we provide a comprehensive review of causal inference methods under the potential outcome framework, one of the well known causal inference framework. The methods are divided into two categories depending on whether they require all three assumptions of the potential outcome framework or not. For each category, both the traditional statistical methods and the recent machine learning enhanced methods are discussed and compared. The plausible applications of these methods are also presented, including the applications in advertising, recommendation, medicine and so on. Moreover, the commonly used benchmark datasets as well as the open-source codes are also summarized, which facilitate researchers and practitioners to explore, evaluate and apply the causal inference methods.
A Survey of Reinforcement Learning Techniques: Strategies, Recent Development, and Future Directions
Reinforcement learning is one of the core components in designing an artificial intelligent system emphasizing real-time response. Reinforcement learning influences the system to take actions within an arbitrary environment either having previous knowledge about the environment model or not. In this paper, we present a comprehensive study on Reinforcement Learning focusing on various dimensions including challenges, the recent development of different state-of-the-art techniques, and future directions. The fundamental objective of this paper is to provide a framework for the presentation of available methods of reinforcement learning that is informative enough and simple to follow for the new researchers and academics in this domain considering the latest concerns. First, we illustrated the core techniques of reinforcement learning in an easily understandable and comparable way. Finally, we analyzed and depicted the recent developments in reinforcement learning approaches. My analysis pointed out that most of the models focused on tuning policy values rather than tuning other things in a particular state of reasoning.
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