Randomized Controlled Trials (RCTs) are the gold standard for evaluating the effect of new medical treatments. Treatments must pass stringent regulatory conditions in order to be approved for widespread use, yet even after the regulatory barriers are crossed, real-world challenges might arise: Who should get the treatment? What is its true clinical utility? Are there discrepancies in the treatment effectiveness across diverse and under-served populations? We introduce two new objectives for future clinical trials that integrate regulatory constraints and treatment policy value for both the entire population and under-served populations, thus answering some of the questions above in advance. Designed to meet these objectives, we formulate Randomize First Augment Next (RFAN), a new framework for designing Phase III clinical trials. Our framework consists of a standard randomized component followed by an adaptive one, jointly meant to efficiently and safely acquire and assign patients into treatment arms during the trial. Then, we propose strategies for implementing RFAN based on causal, deep Bayesian active learning. Finally, we empirically evaluate the performance of our framework using synthetic and real-world semi-synthetic datasets.

Deep Reinforcement Learning is an effective tool for drug dosing for chronic condition management. However, the final protocol is generally a black box without any justification for its prescribed doses. This paper addresses this issue by proposing an explainable dosing protocol for warfarin using a Proximal Policy Optimization method combined with Policy Distillation. We introduce Action Forging as an effective tool to achieve explainability. Our focus is on the maintenance dosing protocol. Results show that the final model is as easy to understand and deploy as the current dosing protocols and outperforms the baseline dosing algorithms.

The ChatGPT, a lite and conversational variant of Generative Pretrained Transformer 4 (GPT-4) developed by OpenAI, is one of the milestone Large Language Models (LLMs) with billions of parameters. LLMs have stirred up much interest among researchers and practitioners in their impressive skills in natural language processing tasks, which profoundly impact various fields. This paper mainly discusses the future applications of LLMs in dentistry. We introduce two primary LLM deployment methods in dentistry, including automated dental diagnosis and cross-modal dental diagnosis, and examine their potential applications. Especially, equipped with a cross-modal encoder, a single LLM can manage multi-source data and conduct advanced natural language reasoning to perform complex clinical operations. We also present cases to demonstrate the potential of a fully automatic Multi-Modal LLM AI system for dentistry clinical application. While LLMs offer significant potential benefits, the challenges, such as data privacy, data quality, and model bias, need further study. Overall, LLMs have the potential to revolutionize dental diagnosis and treatment, which indicates a promising avenue for clinical application and research in dentistry.

Warfarin is a widely used anticoagulant, and has a narrow therapeutic range. Dosing of warfarin should be individualized, since slight overdosing or underdosing can have catastrophic or even fatal consequences. Despite much research on warfarin dosing, current dosing protocols do not live up to expectations, especially for patients sensitive to warfarin. We propose a deep reinforcement learning-based dosing model for warfarin. To overcome the issue of relatively small sample sizes in dosing trials, we use a Pharmacokinetic/ Pharmacodynamic (PK/PD) model of warfarin to simulate dose-responses of virtual patients. Applying the proposed algorithm on virtual test patients shows that this model outperforms a set of clinically accepted dosing protocols by a wide margin. We tested the robustness of our dosing protocol on a second PK/PD model and showed that its performance is comparable to the set of baseline protocols.

In this paper, it has attempted to use Reinforcement learning to model the proper dosage of Warfarin for patients.The paper first examines two baselines: a fixed model of 35 mg/week dosages and a linear model that relies on patient data. We implemented a LinUCB bandit that improved performance measured on regret and percent incorrect. On top of the LinUCB bandit, we experimented with online supervised learning and reward reshaping to boost performance. Our results clearly beat the baselines and show the promise of using multi-armed bandits and artificial intelligence to aid physicians in deciding proper dosages.

This story was originally published by Undark and is reproduced here as part of the Climate Desk collaboration. Early one winter morning in 2020, Kurt VerCauteren discovered a cluster of dead birds in a barren field in northwest Texas. They were small birds, mostly dark-eyed juncos, but also a smattering of white-crowned sparrows. VerCauteren's team had poisoned them, inadvertently. The clues were clear, the death uncomplicated: The birds had flown in before dawn to scavenge deadly morsels of a contaminated peanut paste, left behind after a sounder of wild hogs had torn through the area in a feeding frenzy. The birds likely died within minutes of eating. "I couldn't even see the crumbs," says VerCauteren, a wildlife biologist at the US Department of Agriculture in Fort Collins, Colorado, who has spent years developing and testing pig poisons. The birds were the unintended victims of a field experiment to test a toxicant--one intended for feral pigs, but no other animals--that had been developed in Australia.

Adversarial data poisoning is an effective attack against machine learning and threatens model integrity by introducing poisoned data into the training dataset. So far, it has been studied mostly for classification, even though regression learning is used in many mission critical systems (such as dosage of medication, control of cyber-physical systems and managing power supply). Therefore, in the present research, we aim to evaluate all aspects of data poisoning attacks on regression learning, exceeding previous work both in terms of breadth and depth. We present realistic scenarios in which data poisoning attacks threaten production systems and introduce a novel black-box attack, which is then applied to a real-word medical use-case. As a result, we observe that the mean squared error (MSE) of the regressor increases to 150 percent due to inserting only two percent of poison samples. Finally, we present a new defense strategy against the novel and previous attacks and evaluate it thoroughly on 26 datasets. As a result of the conducted experiments, we conclude that the proposed defence strategy effectively mitigates the considered attacks.

An individualized dose rule recommends a dose level within a continuous safe dose range based on patient level information such as physical conditions, genetic factors and medication histories. Traditionally, personalized dose finding process requires repeating clinical visits of the patient and frequent adjustments of the dosage. Thus the patient is constantly exposed to the risk of underdosing and overdosing during the process. Statistical methods for finding an optimal individualized dose rule can lower the costs and risks for patients. In this article, we propose a kernel assisted learning method for estimating the optimal individualized dose rule. The proposed methodology can also be applied to all other continuous decision-making problems. Advantages of the proposed method include robustness to model misspecification and capability of providing statistical inference for the estimated parameters. In the simulation studies, we show that this method is capable of identifying the optimal individualized dose rule and produces favorable expected outcomes in the population. Finally, we illustrate our approach using data from a warfarin dosing study for thrombosis patients.

Determining the optimal initial dose for warfarin is a critically important task. Several factors have an impact on the therapeutic dose for individual patients, such as patients' physical attributes (Age, Height, etc.), medication profile, co-morbidities, and metabolic genotypes (CYP2C9 and VKORC1). These wide range factors influencing therapeutic dose, create a complex environment for clinicians to determine the optimal initial dose. Using a sample of 4,237 patients, we have proposed a companion classification model to one of the most popular dosing algorithms (International Warfarin Pharmacogenetics Consortium (IWPC) clinical model), which identifies the appropriate cohort of patients for applying this model. The proposed model functions as a clinical decision support system which assists clinicians in dosing. We have developed a classification model using Support Vector Machines, with a polynomial kernel function to determine if applying the dose prediction model is appropriate for a given patient. The IWPC clinical model will only be used if the patient is classified as "Safe for model". By using the proposed methodology, the dosing mode's prediction accuracy increases by 15 percent in terms of Root Mean Squared Error and 17 percent in terms of Mean Absolute Error in dose estimates of patients classified as "Safe for model".

The introduction of data analytics into medicine has changed the nature of patient treatment. In this, patients are asked to disclose personal information such as genetic markers, lifestyle habits, and clinical history. This data is then used by statistical models to predict personalized treatments. However, due to privacy concerns, patients often desire to withhold sensitive information. This self-censorship can impede proper diagnosis and treatment, which may lead to serious health complications and even death over time. In this paper, we present privacy distillation, a mechanism which allows patients to control the type and amount of information they wish to disclose to the healthcare providers for use in statistical models. Meanwhile, it retains the accuracy of models that have access to all patient data under a sufficient but not full set of privacy-relevant information. We validate privacy distillation using a corpus of patients prescribed to warfarin for a personalized dosage. We use a deep neural network to implement privacy distillation for training and making dose predictions. We find that privacy distillation with sufficient privacy-relevant information i) retains accuracy almost as good as having all patient data (only 3\% worse), and ii) is effective at preventing errors that introduce health-related risks (only 3.9\% worse under- or over-prescriptions).