Nina Deliu

Isabel Chien, Nina Deliu, Richard E. Turner et al. · cambridge

While interest in the application of machine learning to improve healthcare has grown tremendously in recent years, a number of barriers prevent deployment in medical practice. A notable concern is the potential to exacerbate entrenched biases and existing health disparities in society. The area of fairness in machine learning seeks to address these issues of equity; however, appropriate approaches are context-dependent, necessitating domain-specific consideration. We focus on clinical trials, i.e., research studies conducted on humans to evaluate medical treatments. Clinical trials are a relatively under-explored application in machine learning for healthcare, in part due to complex ethical, legal, and regulatory requirements and high costs. Our aim is to provide a multi-disciplinary assessment of how fairness for machine learning fits into the context of clinical trials research and practice. We start by reviewing the current ethical considerations and guidelines for clinical trials and examine their relationship with common definitions of fairness in machine learning. We examine potential sources of unfairness in clinical trials, providing concrete examples, and discuss the role machine learning might play in either mitigating potential biases or exacerbating them when applied without care. Particular focus is given to adaptive clinical trials, which may employ machine learning. Finally, we highlight concepts that require further investigation and development, and emphasize new approaches to fairness that may be relevant to the design of clinical trials.

Nina Deliu, Joseph Jay Williams, Bibhas Chakraborty

In recent years, reinforcement learning (RL) has acquired a prominent position in health-related sequential decision-making problems, gaining traction as a valuable tool for delivering adaptive interventions (AIs). However, in part due to a poor synergy between the methodological and the applied communities, its real-life application is still limited and its potential is still to be realized. To address this gap, our work provides the first unified technical survey on RL methods, complemented with case studies, for constructing various types of AIs in healthcare. In particular, using the common methodological umbrella of RL, we bridge two seemingly different AI domains, dynamic treatment regimes and just-in-time adaptive interventions in mobile health, highlighting similarities and differences between them and discussing the implications of using RL. Open problems and considerations for future research directions are outlined. Finally, we leverage our experience in designing case studies in both areas to showcase the significant collaborative opportunities between statistical, RL, and healthcare researchers in advancing AIs.

Harsh Kumar, Tong Li, Jiakai Shi et al.

Digital mental health (DMH) interventions, such as text-message-based lessons and activities, offer immense potential for accessible mental health support. While these interventions can be effective, real-world experimental testing can further enhance their design and impact. Adaptive experimentation, utilizing algorithms like Thompson Sampling for (contextual) multi-armed bandit (MAB) problems, can lead to continuous improvement and personalization. However, it remains unclear when these algorithms can simultaneously increase user experience rewards and facilitate appropriate data collection for social-behavioral scientists to analyze with sufficient statistical confidence. Although a growing body of research addresses the practical and statistical aspects of MAB and other adaptive algorithms, further exploration is needed to assess their impact across diverse real-world contexts. This paper presents a software system developed over two years that allows text-messaging intervention components to be adapted using bandit and other algorithms while collecting data for side-by-side comparison with traditional uniform random non-adaptive experiments. We evaluate the system by deploying a text-message-based DMH intervention to 1100 users, recruited through a large mental health non-profit organization, and share the path forward for deploying this system at scale. This system not only enables applications in mental health but could also serve as a model testbed for adaptive experimentation algorithms in other domains.

Xueqing Liu, Nina Deliu, Tanujit Chakraborty et al.

Mobile health (mHealth) interventions often aim to improve distal outcomes, such as clinical conditions, by optimizing proximal outcomes through just-in-time adaptive interventions. Contextual bandits provide a suitable framework for customizing such interventions according to individual time-varying contexts. However, unique challenges, such as modeling count outcomes within bandit frameworks, have hindered the widespread application of contextual bandits to mHealth studies. The current work addresses this challenge by leveraging count data models into online decision-making approaches. Specifically, we combine four common offline count data models (Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial regressions) with Thompson sampling, a popular contextual bandit algorithm. The proposed algorithms are motivated by and evaluated on a real dataset from the Drink Less trial, where they are shown to improve user engagement with the mHealth platform. The proposed methods are further evaluated on simulated data, achieving improvement in maximizing cumulative proximal outcomes over existing algorithms. Theoretical results on regret bounds are also derived. The countts R package provides an implementation of our approach.

Nina Deliu, Bibhas Chakraborty

Precision health, increasingly supported by digital technologies, is a domain of research that broadens the paradigm of precision medicine, advancing everyday healthcare. This vision goes hand in hand with the groundbreaking advent of artificial intelligence (AI), which is reshaping the way we diagnose, treat, and monitor both clinical subjects and the general population. AI tools powered by machine learning have shown considerable improvements in a variety of healthcare domains. In particular, reinforcement learning (RL) holds great promise for sequential and dynamic problems such as dynamic treatment regimes and just-in-time adaptive interventions in digital health. In this work, we discuss the opportunity offered by AI, more specifically RL, to current trends in healthcare, providing a methodological survey of RL methods in the context of precision and digital health. Focusing on the area of adaptive interventions, we expand the methodological survey with illustrative case studies that used RL in real practice. This invited article has undergone anonymous review and is intended as a book chapter for the volume "Frontiers of Statistics and Data Science" edited by Subhashis Ghoshal and Anindya Roy for the International Indian Statistical Association Series on Statistics and Data Science, published by Springer. It covers the material from a short course titled "Artificial Intelligence in Precision and Digital Health" taught by the author Bibhas Chakraborty at the IISA 2022 Conference, December 26-30 2022, at the Indian Institute of Science, Bengaluru.

Simone Cuonzo, Nina Deliu

We introduce Conformal Bandits, a novel framework integrating Conformal Prediction (CP) into bandit problems, a classic paradigm for sequential decision-making under uncertainty. Traditional regret-minimisation bandit strategies like Thompson Sampling and Upper Confidence Bound (UCB) typically rely on distributional assumptions or asymptotic guarantees; further, they remain largely focused on regret, neglecting their statistical properties. We address this gap. Through the adoption of CP, we bridge the regret-minimising potential of a decision-making bandit policy with statistical guarantees in the form of finite-time prediction coverage. We demonstrate the potential of it Conformal Bandits through simulation studies and an application to portfolio allocation, a typical small-gap regime, where differences in arm rewards are far too small for classical policies to achieve optimal regret bounds in finite sample. Motivated by this, we showcase our framework's practical advantage in terms of regret in small-gap settings, as well as its added value in achieving nominal coverage guarantees where classical UCB policies fail. Focusing on our application of interest, we further illustrate how integrating hidden Markov models to capture the regime-switching behaviour of financial markets, enhances the exploration-exploitation trade-off, and translates into higher risk-adjusted regret efficiency returns, while preserving coverage guarantees.

Amy Armento Lee, Narayan Hegde, Nina Deliu et al.

Consistent physical inactivity poses a major global health challenge. Mobile health (mHealth) interventions, particularly Just-in-Time Adaptive Interventions (JITAIs), offer a promising avenue for scalable, personalized physical activity (PA) promotion. However, developing and evaluating such interventions at scale, while integrating robust behavioral science, presents methodological hurdles. The PEARL study was the first large-scale, four-arm randomized controlled trial to assess a reinforcement learning (RL) algorithm, informed by health behavior change theory, to personalize the content and timing of PA nudges via a Fitbit app. We enrolled and randomized 13,463 Fitbit users into four study arms: control, random, fixed, and RL. The control arm received no nudges. The other three arms received nudges from a bank of 155 nudges based on behavioral science principles. The random arm received nudges selected at random. The fixed arm received nudges based on a pre-set logic from survey responses about PA barriers. The RL group received nudges selected by an adaptive RL algorithm. We included 7,711 participants in primary analyses (mean age 42.1, 86.3% female, baseline steps 5,618.2). We observed an increase in PA for the RL group compared to all other groups from baseline to 1 and 2 months. The RL group had significantly increased average daily step count at 1 month compared to all other groups: control (+296 steps, p=0.0002), random (+218 steps, p=0.005), and fixed (+238 steps, p=0.002). At 2 months, the RL group sustained a significant increase compared to the control group (+210 steps, p=0.0122). Generalized estimating equation models also revealed a sustained increase in daily steps in the RL group vs. control (+208 steps, p=0.002). These findings demonstrate the potential of a scalable, behaviorally-informed RL approach to personalize digital health interventions for PA.

Tong Li, Jacob Nogas, Haochen Song et al.

Traditional randomized A/B experiments assign arms with uniform random (UR) probability, such as 50/50 assignment to two versions of a website to discover whether one version engages users more. To more quickly and automatically use data to benefit users, multi-armed bandit algorithms such as Thompson Sampling (TS) have been advocated. While TS is interpretable and incorporates the randomization key to statistical inference, it can cause biased estimates and increase false positives and false negatives in detecting differences in arm means. We introduce a more Statistically Sensitive algorithm, TS-PostDiff (Posterior Probability of Small Difference), that mixes TS with traditional UR by using an additional adaptive step, where the probability of using UR (vs TS) is proportional to the posterior probability that the difference in arms is small. This allows an experimenter to define what counts as a small difference, below which a traditional UR experiment can obtain informative data for statistical inference at low cost, and above which using more TS to maximize user benefits is key. We evaluate TS-PostDiff against UR, TS, and two other TS variants designed to improve statistical inference. We consider results for the common two-armed experiment across a range of settings inspired by real-world applications. Our results provide insight into when and why TS-PostDiff or alternative approaches provide better tradeoffs between benefiting users (reward) and statistical inference (false positive rate and power). TS-PostDiff's adaptivity helps efficiently reduce false positives and increase statistical power when differences are small, while increasing reward more when differences are large. The work highlights important considerations for future Statistically Sensitive algorithm development that balances reward and statistical analysis in adaptive experimentation.

Nina Deliu, Joseph J. Williams, Sofia S. Villar

Using bandit algorithms to conduct adaptive randomised experiments can minimise regret, but it poses major challenges for statistical inference (e.g., biased estimators, inflated type-I error and reduced power). Recent attempts to address these challenges typically impose restrictions on the exploitative nature of the bandit algorithm$-$trading off regret$-$and require large sample sizes to ensure asymptotic guarantees. However, large experiments generally follow a successful pilot study, which is tightly constrained in its size or duration. Increasing power in such small pilot experiments, without limiting the adaptive nature of the algorithm, can allow promising interventions to reach a larger experimental phase. In this work we introduce a novel hypothesis test, uniquely based on the allocation probabilities of the bandit algorithm, and without constraining its exploitative nature or requiring a minimum experimental size. We characterise our $Allocation\ Probability\ Test$ when applied to $Thompson\ Sampling$, presenting its asymptotic theoretical properties, and illustrating its finite-sample performances compared to state-of-the-art approaches. We demonstrate the regret and inferential advantages of our approach, particularly in small samples, in both extensive simulations and in a real-world experiment on mental health aspects.

Joseph Jay Williams, Jacob Nogas, Nina Deliu et al.

Multi-armed bandit algorithms have been argued for decades as useful for adaptively randomized experiments. In such experiments, an algorithm varies which arms (e.g. alternative interventions to help students learn) are assigned to participants, with the goal of assigning higher-reward arms to as many participants as possible. We applied the bandit algorithm Thompson Sampling (TS) to run adaptive experiments in three university classes. Instructors saw great value in trying to rapidly use data to give their students in the experiments better arms (e.g. better explanations of a concept). Our deployment, however, illustrated a major barrier for scientists and practitioners to use such adaptive experiments: a lack of quantifiable insight into how much statistical analysis of specific real-world experiments is impacted (Pallmann et al, 2018; FDA, 2019), compared to traditional uniform random assignment. We therefore use our case study of the ubiquitous two-arm binary reward setting to empirically investigate the impact of using Thompson Sampling instead of uniform random assignment. In this setting, using common statistical hypothesis tests, we show that collecting data with TS can as much as double the False Positive Rate (FPR; incorrectly reporting differences when none exist) and the False Negative Rate (FNR; failing to report differences when they exist)...