Designing and evaluating an online reinforcement learning agent for physical exercise recommendations in N-of-1 trials

Personalized adaptive interventions offer the opportunity to increase patient benefits, however, there are challenges in their planning and implementation. Once implemented, it is an important question whether personalized adaptive interventions are indeed clinically more effective compared to a fixed gold standard intervention. In this paper, we present an innovative N-of-1 trial study design testing whether implementing a personalized intervention by an online reinforcement learning agent is feasible and effective. Throughout, we use a new study on physical exercise recommendations to reduce pain in endometriosis for illustration. We describe the design of a contextual bandit recommendation agent and evaluate the agent in simulation studies. The results show that adaptive interventions add complexity to the design and implementation process, but have the potential to improve patients' benefits even if only few observations are available. In order to quantify the expected benefit, data from previous interventional studies is required. We expect our approach to be transferable to other interventions and clinical interventions.

StudyMe: A New Mobile App for User-Centric N-of-1 Trials

N-of-1 trials are multi-crossover self-experiments that allow individuals to systematically evaluate the effect of interventions on their personal health goals. Although several tools for N-of-1 trials exist, none support non-experts in conducting their own user-centric trials. In this study we present StudyMe, an open-source mobile application that is freely available from https://play.google.com/store/apps/details?id=health.studyu.me and offers users flexibility and guidance in configuring every component of their trials. We also present research that informed the development of StudyMe. Through an initial survey with 272 participants, we learned that individuals are interested in a variety of personal health aspects and have unique ideas on how to improve them. In an iterative, user-centered development process with intermediate user tests we developed StudyMe that also features an educational part to communicate N-of-1 trial concepts. A final empirical evaluation of StudyMe showed that all participants were able to create their own trials successfully using StudyMe and the app achieved a very good usability rating. Our findings suggest that StudyMe provides a significant step towards enabling individuals to apply a systematic science-oriented approach to personalize health-related interventions and behavior modifications in their everyday lives.

Integrating omics and MRI data with kernel-based tests and CNNs to identify rare genetic markers for Alzheimer's disease

For precision medicine and personalized treatment, we need to identify predictive markers of disease. We focus on Alzheimer's disease (AD), where magnetic resonance imaging scans provide information about the disease status. By combining imaging with genome sequencing, we aim at identifying rare genetic markers associated with quantitative traits predicted from convolutional neural networks (CNNs), which traditionally have been derived manually by experts. Kernel-based tests are a powerful tool for associating sets of genetic variants, but how to optimally model rare genetic variants is still an open research question. We propose a generalized set of kernels that incorporate prior information from various annotations and multi-omics data. In the analysis of data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we evaluate whether (i) CNNs yield precise and reliable brain traits, and (ii) the novel kernel-based tests can help to identify loci associated with AD. The results indicate that CNNs provide a fast, scalable and precise tool to derive quantitative AD traits and that new kernels integrating domain knowledge can yield higher power in association tests of very rare variants.