Rachael V. Phillips

Ivana Malenica, Rachael V. Phillips, Daniel Lazzareschi et al.

We propose a novel, fully nonparametric approach for the multi-task learning, the Multi-task Highly Adaptive Lasso (MT-HAL). MT-HAL simultaneously learns features, samples and task associations important for the common model, while imposing a shared sparse structure among similar tasks. Given multiple tasks, our approach automatically finds a sparse sharing structure. The proposed MTL algorithm attains a powerful dimension-free convergence rate of $o_p(n^{-1/4})$ or better. We show that MT-HAL outperforms sparsity-based MTL competitors across a wide range of simulation studies, including settings with nonlinear and linear relationships, varying levels of sparsity and task correlations, and different numbers of covariates and sample size.

Ahmed Alaa, Rachael V. Phillips, Emre Kıcıman et al.

The validity of medical studies based on real-world clinical data, such as observational studies, depends on critical assumptions necessary for drawing causal conclusions about medical interventions. Many published studies are flawed because they violate these assumptions and entail biases such as residual confounding, selection bias, and misalignment between treatment and measurement times. Although researchers are aware of these pitfalls, they continue to occur because anticipating and addressing them in the context of a specific study can be challenging without a large, often unwieldy, interdisciplinary team with extensive expertise. To address this expertise gap, we explore the use of large language models (LLMs) as co-pilot tools to assist researchers in identifying study design flaws that undermine the validity of causal inferences. We propose a conceptual framework for LLMs as causal co-pilots that encode domain knowledge across various fields, engaging with researchers in natural language interactions to provide contextualized assistance in study design. We provide illustrative examples of how LLMs can function as causal co-pilots, propose a structured framework for their grounding in existing causal inference frameworks, and highlight the unique challenges and opportunities in adapting LLMs for reliable use in epidemiological research.

Philippe E. Spiess, Md Muntasir Zitu, Alison Walker et al.

Background: More than 80% of U.S. cancer care is delivered in community settings, where survival remains worse than at academic centers. Clinicians must integrate genomics, staging, radiology, pathology, and changing guidelines, creating cognitive burden. We evaluated OncoBrain, an AI clinical reasoning platform for oncology treatment-plan generation, as an early step toward OGI. Methods: OncoBrain combines general-purpose LLMs with a cancer-specific graph retrieval-augmented generation layer, a gold-standard treatment-plan corpus as long-term memory, and a model-agnostic safety layer (CHECK) for hallucination detection and suppression. We evaluated clinician-enriched case summaries across gynecologic, genitourinary, neuro-oncology, gastrointestinal/hepatobiliary, and hematologic malignancies. Three clinician groups completed structured evaluations of 173 cases using a common 16-item instrument: subspecialist oncologists reviewed 50 cases, physician reviewers 78, and advanced practice providers 45. Results: Ratings were highest for scientific accuracy, evidence support, and safety, with lower but favorable scores for workflow integration and time savings. On a 5-point scale, mean alignment with evidence and guidelines was 4.60, 4.56, and 4.70 across subspecialists, physician reviewers, and advanced practice providers. Mean scores for absence of safety or misinformation concerns were 4.80, 4.40, and 4.60. Workflow integration averaged 4.50, 3.94, and 4.00; perceived time savings averaged 5.00, 3.89, and 3.60. Conclusions: In this multi-specialty vignette-based evaluation, OncoBrain generated oncology treatment plans judged guideline-concordant, clinically acceptable, and easy to supervise. These findings support the potential of a carefully engineered AI reasoning platform to assist oncology treatment planning and justify prospective real-world evaluation in community settings.

Ivana Malenica, Rachael V. Phillips, Romain Pirracchio et al.

In this work, we introduce the Personalized Online Super Learner (POSL) -- an online ensembling algorithm for streaming data whose optimization procedure accommodates varying degrees of personalization. Namely, POSL optimizes predictions with respect to baseline covariates, so personalization can vary from completely individualized (i.e., optimization with respect to baseline covariate subject ID) to many individuals (i.e., optimization with respect to common baseline covariates). As an online algorithm, POSL learns in real-time. POSL can leverage a diversity of candidate algorithms, including online algorithms with different training and update times, fixed algorithms that are never updated during the procedure, pooled algorithms that learn from many individuals' time-series, and individualized algorithms that learn from within a single time-series. POSL's ensembling of this hybrid of base learning strategies depends on the amount of data collected, the stationarity of the time-series, and the mutual characteristics of a group of time-series. In essence, POSL decides whether to learn across samples, through time, or both, based on the underlying (unknown) structure in the data. For a wide range of simulations that reflect realistic forecasting scenarios, and in a medical data application, we examine the performance of POSL relative to other current ensembling and online learning methods. We show that POSL is able to provide reliable predictions for time-series data and adjust to changing data-generating environments. We further cultivate POSL's practicality by extending it to settings where time-series enter/exit dynamically over chronological time.

Jeremy R. Coyle, Nima S. Hejazi, Ivana Malenica et al.

Targeted Learning is a subfield of statistics that unifies advances in causal inference, machine learning and statistical theory to help answer scientifically impactful questions with statistical confidence. Targeted Learning is driven by complex problems in data science and has been implemented in a diversity of real-world scenarios: observational studies with missing treatments and outcomes, personalized interventions, longitudinal settings with time-varying treatment regimes, survival analysis, adaptive randomized trials, mediation analysis, and networks of connected subjects. In contrast to the (mis)application of restrictive modeling strategies that dominate the current practice of statistics, Targeted Learning establishes a principled standard for statistical estimation and inference (i.e., confidence intervals and p-values). This multiply robust approach is accompanied by a guiding roadmap and a burgeoning software ecosystem, both of which provide guidance on the construction of estimators optimized to best answer the motivating question. The roadmap of Targeted Learning emphasizes tailoring statistical procedures so as to minimize their assumptions, carefully grounding them only in the scientific knowledge available. The end result is a framework that honestly reflects the uncertainty in both the background knowledge and the available data in order to draw reliable conclusions from statistical analyses - ultimately enhancing the reproducibility and rigor of scientific findings.