Harmonizing Safety and Speed: A Human-Algorithm Approach to Enhance the FDA's Medical Device Clearance Policy

The United States Food and Drug Administration's (FDA's) Premarket Notification 510(K) pathway allows manufacturers to gain approval for a medical device by demonstrating its substantial equivalence to another legally marketed device. However, the inherent ambiguity of this regulatory procedure has led to high recall rates for many devices cleared through this pathway. This trend has raised significant concerns regarding the efficacy of the FDA's current approach, prompting a reassessment of the 510(K) regulatory framework. In this paper, we develop a combined human-algorithm approach to assist the FDA in improving its 510(k) medical device clearance process by reducing the risk of potential recalls and the workload imposed on the FDA. We first develop machine learning methods to estimate the risk of recall of 510(k) medical devices based on the information available at the time of submission. We then propose a data-driven clearance policy that recommends acceptance, rejection, or deferral to FDA's committees for in-depth evaluation. We conduct an empirical study using a unique large-scale dataset of over 31,000 medical devices and 12,000 national and international manufacturers from over 65 countries that we assembled based on data sources from the FDA and Centers for Medicare and Medicaid Service (CMS). A conservative evaluation of our proposed policy based on this data shows a 38.9% improvement in the recall rate and a 43.0% reduction in the FDA's workload. Our analyses also indicate that implementing our policy could result in significant annual cost-savings ranging between \$2.4 billion and \$2.7 billion, which highlights the value of using a holistic and data-driven approach to improve the FDA's current 510(K) medical device evaluation pathway.

Effective Generative AI: The Human-Algorithm Centaur

Advanced analytics science methods have enabled combining the power of artificial and human intelligence, creating \textit{centaurs} that allow superior decision-making. Centaurs are hybrid human-algorithm AI models that combine both formal analytics and human intuition in a symbiotic manner within their learning and reasoning process. We argue that the future of AI development and use in many domains needs to focus on centaurs as opposed to traditional AI approaches. This paradigm shift from traditional AI methods to centaur-based AI methods raises some fundamental questions: How are centaurs different from traditional human-in-the-loop methods? What are the most effective methods for creating centaurs? When should centaurs be used, and when should the lead be given to traditional AI models? Doesn't the incorporation of human intuition -- which at times can be misleading -- in centaurs' decision-making process degrade its performance compared to traditional AI methods? This work aims to address these fundamental questions, focusing on recent advancements in generative AI, and especially in Large Language Models (LLMs), as a main case study to illustrate centaurs' critical essentiality to future AI endeavors.

Ambiguous Dynamic Treatment Regimes: A Reinforcement Learning Approach

A main research goal in various studies is to use an observational data set and provide a new set of counterfactual guidelines that can yield causal improvements. Dynamic Treatment Regimes (DTRs) are widely studied to formalize this process. However, available methods in finding optimal DTRs often rely on assumptions that are violated in real-world applications (e.g., medical decision-making or public policy), especially when (a) the existence of unobserved confounders cannot be ignored, and (b) the unobserved confounders are time-varying (e.g., affected by previous actions). When such assumptions are violated, one often faces ambiguity regarding the underlying causal model that is needed to be assumed to obtain an optimal DTR. This ambiguity is inevitable, since the dynamics of unobserved confounders and their causal impact on the observed part of the data cannot be understood from the observed data. Motivated by a case study of finding superior treatment regimes for patients who underwent transplantation in our partner hospital and faced a medical condition known as New Onset Diabetes After Transplantation (NODAT), we extend DTRs to a new class termed Ambiguous Dynamic Treatment Regimes (ADTRs), in which the casual impact of treatment regimes is evaluated based on a "cloud" of potential causal models. We then connect ADTRs to Ambiguous Partially Observable Mark Decision Processes (APOMDPs) proposed by Saghafian (2018), and develop two Reinforcement Learning methods termed Direct Augmented V-Learning (DAV-Learning) and Safe Augmented V-Learning (SAV-Learning), which enable using the observed data to efficiently learn an optimal treatment regime. We establish theoretical results for these learning methods, including (weak) consistency and asymptotic normality. We further evaluate the performance of these learning methods both in our case study and in simulation experiments.