Counterfactual Prediction

Covariate-aware time-series foundation models (TSFMs) promise training-free what-if answers for instrumented plants: the change in output that a different future input would cause. We test this on forced engineering systems with exact counterfactuals, comparing Chronos-2, TimesFM-2.5 and TabPFN-TS with classical system identification fitted to the same context. Through their default covariate interfaces, TimesFM-2.5 and TabPFN-TS are memoryless: the predicted effect of an input change is a same-time function of that change ($R^2 = 1.000$ for TimesFM-2.5). Chronos-2 identifies dynamics in context but attenuates them. Its predicted effect is 0.33-0.80 of the true effect, its recovered impulse response has the wrong shape, and its error on a one-degree-of-freedom oscillator levels off at 0.57 with 8192 context samples, where ARX fitted to 256 samples reaches 0.02. Context dither at inference lowers the what-if error on all six synthetic classes without training. A 26-minute fine-tune on synthetic forced systems restores the response magnitude (sensitivity 0.83-0.96) and outperforms structure-agnostic identification on Wiener-Hammerstein and a held-out friction class. A specialised in-context identifier trained on the same data comes close, so the forced-system data carry most of the gain. On three of four measured plants classical identification remains clearly better, and the fine-tuned model loses part of its univariate forecasting skill. Paired counterfactual inputs, together with shuffled future inputs on measured records, test two properties: whether the covariate interface can represent dynamics and whether the pretraining prior covers the plant's time scale. Only the counterfactual pairs expose the attenuation.

A learned simulator can reproduce its training conditions accurately yet fail in two distinct ways once those conditions change. Over long rollouts, small errors accumulate until the trajectory drifts away from physically plausible behavior; under an intervention on a physical parameter, the model may continue to follow the law seen during training rather than the intervened one. We show that these two failures require different structural remedies. Evolving a learned energy with a symplectic integrator preserves the geometry of the conservative dynamics and keeps rollouts bounded and physically meaningful for up to $100\times$ the training horizon, while equal-capacity predictors, an energy-regularized predictor, and a tuned neural ODE diverge. By contrast, encoding the physical coupling through an explicit linear factorization enables the model to follow a never-seen sign of that coupling, whereas an unrestricted parameterization remains locked to the training law. Crucially, the two mechanisms are separable: removing the structure responsible for long-horizon stability leaves counterfactual transfer intact, while removing the factorized coupling destroys counterfactual transfer without eliminating stability. This double dissociation, established with matched controls that remove or replace one structural component at a time, persists beyond the headline three-body system and remains visible when the physical state must be inferred from pixels rather than provided directly. The result is a concrete design principle for physical world models: long-horizon stability and changed-law generalization arise from distinct structural commitments, and each can be imposed deliberately without requiring the other.

Deep Limit Order Book forecasting models capture nonlinear market dynamics, but their ability to quantify the effects of counterfactual order book messages has not been systematically validated. We introduce a model-agnostic framework that compares a trained forecaster's predictive distributions before and after injecting mechanically valid counterfactual messages, defining short-horizon model-implied market impact. A Transformer-based forecaster recovered scenario rankings with a Spearman correlation of 0.99 and 97.2% directional agreement with realized historical outcomes among non-neutral scenarios. Observation-level analysis further showed that estimated impacts captured incremental sequence-dependent variation beyond scenario identity and the pre-event forecast. These results provide evidence that pretrained Limit Order Book forecasters can be repurposed for scenario-conditioned response modeling without retraining.

Conformal counterfactual prediction constructs prediction sets with finite-sample coverage guarantees for counterfactual outcomes and individual treatment effects under the no-interference assumption. In this work, we relax this assumption by allowing each unit's potential outcomes to depend on other units' treatments and covariates. In this setting, propensity-score reweighting does not restore weighted exchangeability, and existing methods may fail to achieve valid coverage. To address this issue, we develop interference-adjusted weighted conformal prediction that accounts for interference by constructing an observable upper bound on the ideal and unobserved conformal $p$-value under the target intervention. The resulting prediction sets provide finite-sample marginal coverage guarantees for counterfactual outcomes and individual treatment effects in both transductive and inductive settings. We also derive a sharper construction when intervention-induced changes in nonconformity scores are bounded. Numerical experiments show that our methods preserve nominal coverage, whereas existing methods may not.

Clinical prediction models are often developed as if the outcome of interest were cleanly observed for every patient. This assumption fails when treatment decisions make the clinically relevant outcome permanently unobservable. As a case study of this problem, we consider post-cardiac-arrest neurological prognostication using a cohort of 2,497 patients, including 1,429 patients whose outcomes were rendered indeterminate by treatment decisions. These patients with indeterminate outcomes were reviewed by independent clinical experts, who provided their guesses of counterfactual outcomes about what would have happened to the patients. We refer to these patients as uncertain cases. We also have patients for whom we observe their clinically relevant outcomes; we refer to these patients as certain cases. We propose a framework for evaluating prediction models that explicitly splits the evaluation between certain and uncertain cases. Here, we cannot easily evaluate both types of cases in a uniform manner as the available target labels differ. We then propose a simple prediction model that uses target labels from both certain and uncertain cases in a manner that allows us to trade off between them. Across the proposed neural model and a collection of tabular baselines, models with similar certain-case AUROC can nevertheless differ substantially in both certain-case Brier score and their probability estimates for uncertain cases. Improving alignment with target labels of uncertain cases for our proposed model generally comes at the cost of worse accuracy on certain cases, highlighting an explicit tradeoff that standard evaluation conceals. These results show that when treatment decisions determine whether clinically meaningful outcomes remain observable, conventional evaluation metrics can miss important failure modes in the very patients for whom prognostic support matters most.

Driving world models are often interpreted as counterfactual simulators for observed driving episodes: given a factual driving log, they are asked what would have happened under an alternative ego action. In this paper, we identify a fundamental mismatch between this goal and direct action-conditioned prediction. The direct prediction uses the shared history and the alternative action but not the factual continuation observed after that history. It can therefore generate a plausible future without preserving what actually happened in this episode. We formalize this gap using the causal recipe of abduction, action, and prediction and study it in a setting with a short time horizon, where the alternative ego action does not alter how surrounding agents evolve. To make the gap measurable, we construct a controlled simulation benchmark with factual outcomes and matched counterfactual outcomes. Across two representative world models, direct predictions fail to match the counterfactual ground truth, supporting our analysis. As a constructive check of this analysis, we introduce a deliberately simple, training-free pipeline that moves observed evidence into the counterfactual view and lets the frozen model complete what remains unknown. Even this simple construction raises the overall recovered fraction substantially and reduces perceptual distance to the matched counterfactual on both models. We hope this work draws attention to this gap and motivates better counterfactual prediction methods for driving world models.

Estimating counterfactual outcomes over time from longitudinal observational data is central to clinical decision support. Existing methods rely on domain confusion -- adversarial training that renders representations invariant to treatment assignment -- yet this invariance creates a mutual information conflict: it suppresses treatment-correlated covariate signals necessary for accurate outcome prediction. We formalise this tension via a Jensen-Shannon divergence bound on counterfactual prediction error and develop two complementary models. CSSD (Causal State-Space model with Direct decoder) adapts selective State Space Models with a parallel multi-step decoder that eliminates accumulated rollout error by producing all prediction horizons simultaneously in a single forward pass. CSSPD (Causal State-Space model with Predictive regularisation and Direct decoder) augments CSSD with Contrastive Predictive Coding and Local Information Maximisation to reinforce temporal predictability in the balancing representation and recover local covariate information destroyed by domain confusion. On MIMIC-III, CSSPD achieves lower counterfactual RMSE than the Causal Transformer at every horizon tau >= 2 at O(T) encoder cost, with gains from 0.02 (2-step) to 0.07 (6-step). On Cancer Simulation across confounding strengths gamma in {0,1,2,3,4}, CSSPD outperforms CT at gamma <= 3 (margins 25.9%--37.0%), and CSSD achieves the lowest overall average RMSE (12.7% reduction over CT), confirming the MI conflict analysis. To our knowledge, this is the first work to formalise the balancing-prediction MI conflict and propose a structured resolution through complementary predictive and information-theoretic training objectives.

Counterfactual analysis aims to predict potential outcomes under hypothetical scenarios, offering valuable insights for decision-making. This paper investigates the application of large language models (LLMs), specifically the GPT-3.5 model, for counterfactual analysis. We focus on the online lending context, where the counterfactual return on investment (ROI) is crucial for evaluating different interest rate schemes. We begin by assessing the predictive performance of GPT and comparing it with advanced machine learning algorithms. The results show that prompt engineering can significantly enhance GPT's predictions, with the R-squared increasing from 1.97% to 2.84%, closely approaching the 3.48% achieved by gradient-boosted regression. Subsequently, we utilize GPT to generate counterfactual ROIs under a set of alternative interest rates. GPT exhibits logical coherence and causal reasoning in its responses. The findings underscore the potential of LLMs as effective tools for counterfactual analysis in online lending, suggesting broader applications for LLMs in various predictive and decision-making contexts.

There has been significant interest in using machine learning algorithms to predict kidney transplant outcomes, such as the number of years until a graft inevitably fails. These prediction algorithms could possibly be used for pre-transplant donor-recipient matching to identify more compatible donors and recipients and thus improve post-transplant outcomes. In this study, we explore the use of survival prediction models trained on deceased donor kidney transplant data from the Scientific Registry of Transplant Recipients (SRTR). We propose a novel paired recipient-based evaluation framework that compares graft outcomes between two recipients who received kidneys from the same deceased donor, allowing us to evaluate the counterfactual benefit of changing the recipient for a certain donor. We find that five different survival prediction models, ranging in complexity from linear to deep learning-based models, all result in ~60% paired recipient-based accuracy. We further translate this accuracy into an interpretable quantity of post-transplant years gained. We also highlight major limitations of the commonly used concordance index (C-index) metric for evaluating survival prediction accuracy in this setting and demonstrate that our proposed paired recipient-based accuracy metric is more clinically relevant and better reflects real-world allocation settings.

Forecasting benchmarks for general-purpose AI systems usually inherit the constraints of the real world: outcomes resolve slowly, tail events are rare, and counterfactual questions are difficult to score. We introduce ForecastBench-Sim, a simulated-world forecasting benchmark built on game rollouts from Freeciv, a turn-based strategy game modelled on the Civilization series. Forecasters receive a fixed world report (a structured snapshot of the current game state) and answer questions about hidden future states; the benchmark then continues the simulation and scores forecasts. Because the world is simulated, the same setup can generate continuous or binary forecasting questions at arbitrary time horizons, paired intervention worlds for conditional or causal questions, and resolved examples of rare or disruptive outcomes. We describe the benchmark pipeline, question families, scoring protocol, and release artifacts, and report validation slices from model evaluations and an anonymized human pilot. ForecastBench-Sim is intended to complement real-world forecasting benchmarks by providing controlled, immediately resolvable tasks for studying probabilistic reasoning under dynamic world states.

Reliable operation of multi-agent large language model (LLM) systems depends on debugging long execution traces, where the few causally decisive events are buried in unstructured logs of messages, routes, memory writes, and tool calls. The standard tool is counterfactual replay (rewind, edit, and re-run the trajectory to measure each event's effect), but its cost grows linearly with the number of candidate events, making exhaustive replay infeasible at scale. We frame trace debugging as a knowledge-based decision-support problem. Each trace is compiled into a structured event knowledge graph over routing, memory, tool-use, uncertainty, and latent evidence, and a calibrated predictor decides where a scarce replay budget should be spent. We do not propose a new replay oracle; we propose a method to predict its results without paying the replay cost. We formulate zero-replay counterfactual-effect prediction: given a trace under a fixed budget, predict which events the oracle would mark high-effect before any replay is performed. BranchPoint-Latent is a lightweight predictor over observable, structural, uncertainty, and latent features of the knowledge graph. Calibrated against a deterministic replay oracle across 37 trace families, a single learning-to-rank gradient-boosted predictor raises per-trace localization (Branch Recall@5) from 0.73 to 0.93 on held-out families at zero oracle-replay cost. Rather than claiming universal dominance, we characterize when cheap graph centrality suffices and when learned evidence is necessary. The result is an auditable, cost-efficient decision-support system for AI-reliability debugging, positioned explicitly on the cost-accuracy frontier with reproducible artifacts.

Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

Longitudinal treatment decisions from multivariate time-series data require predicting potential outcomes under future treatment sequences in the presence of time-varying confounding, heterogeneous patient dynamics, and limited domain-specific data. Existing longitudinal causal estimators typically address this problem by training a new model for each cohort or simulator. We introduce Causal Longitudinal Prior-Fitted Networks (CausalLongPFN), a prior-fitted network for time-series causal inference in longitudinal treatment-response data and zero-shot in-context counterfactual outcome prediction. The model is pretrained entirely on synthetic episodes sampled from a broad prior over temporal structural causal models, exposing it to treatment-confounder feedback, latent heterogeneity, nonlinear state evolution, delayed effects, and cumulative treatment responses. At test time, CausalLongPFN remains frozen and is used zero-shot: it conditions on support trajectories, a query history, and a planned future treatment sequence, and returns a predictive distribution over future outcomes without gradient updates or propensity-model fitting. Multi-step predictions are obtained by recursively applying the one-step predictor under the specified treatment sequence. We evaluate the model on branchable cancer, HIV, and warfarin benchmarks with ground-truth counterfactual labels, and on factual-only rolling-origin prediction in MIMIC-III ICU trajectories. CausalLongPFN is competitive with domain-trained longitudinal baselines on counterfactual benchmarks and performs strongly on factual MIMIC-III prediction, suggesting that broad synthetic causal pretraining can provide a frozen, amortized alternative for zero-shot longitudinal treatment-response prediction when repeated domain-specific training is costly or impractical.

Deep learning has enabled significant advances in time-series causal inference, yet progress remains constrained by the lack of realistic benchmarks with observable counterfactual outcomes. Existing datasets either rely on real-world observations without ground-truth counterfactuals or on simplified simulations that fail to capture complex causal dynamics. To address this gap, we develop a large-scale benchmark for counterfactual prediction in epidemic time series under dynamic interventions. Unlike existing benchmarks, it supports static and time-varying treatments, as well as both single-policy and multi-policy intervention settings, enabling evaluation of causal inference methods across a broad range of causal inference scenarios. Leveraging a calibrated agent-based model grounded in real-world demographic, mobility, epidemiological, and policy data, we generate realistic counterfactual trajectories across more than 150 U.S. counties. Using this benchmark, we evaluate widely used and state-of-the-art causal inference methods, revealing substantial performance differences and highlighting the challenges of realistic time-series causal reasoning.

Reliable proactive agents must choose an action and judge whether current evidence is sufficient to act. We study retail service from sparse third-person video: before an explicit customer request, an agent must use limited human-object interaction evidence to intervene or remain silent. Physical grounding here means converting observations into task-relevant retail state, not modeling low-level dynamics. We introduce the Proactive Intent World Model (PIWM): See constructs the perceptual basis, Foresee models counterfactual consequences, and Act selects an action. Performance is poor when the agent must extract information from raw video and decide directly, but improves substantially with structured inputs extracted and annotated from a professional retail perspective. AIDA-stage constraints and BDI-state ablations further support role- and goal-directed selection and organization of decision-relevant cues. Counterfactual prediction performs well in standalone evaluation, yet planning methods that query these forecasts at inference time degrade sharply: locally useful consequence prediction does not reliably improve action selection. This gap may reflect incomplete process understanding, uncertainty in fine-grained single-step outcomes, and insufficient joint modeling of scenes and temporal evolution. Hold remains the hardest action in structured-state evaluation, exposing a related challenge in temporal awareness. PIWM advances static intent recognition toward intent world modeling by organizing observations under task knowledge, anticipating candidate interventions, and treating intervention and non-intervention jointly. Future work will introduce long-horizon interaction trajectories and temporal consequence supervision to improve sustained reasoning and intervention timing.

Epidemic forecasting faces a fundamental challenge: human behavior dynamically responds to disease spread, creating feedback loops that induce distribution shifts at policy intervention points. This renders data-driven models unreliable under distribution shift. We propose \textbf{SL-BiLEM} (Structured Learnable Behavior-in-the-Loop Epidemic Model), leveraging physical constraints as regularization for robust extrapolation. The framework decomposes effective transmission as $β_{\text{eff}}(t,g) = β_0(g) \times m_{\text{policy}}(t) \times m_{\text{media}}(t) \times m_{\text{comp}}(t,g)$, where monotonicity, smoothness, and bounded-jump constraints on the learned compliance function maintain predictive validity under novel policy regimes. Beyond forecasting, SL-BiLEM enables counterfactual analysis for intervention decision support. We validate forecasting on three real-world datasets (cruise ship, school influenza, and school-district COVID-19 surveillance) and evaluate counterfactual recovery on synthetic benchmarks with known ground truth. SL-BiLEM demonstrates: (1) 76% improvement over neural-mechanistic baselines, with only 53% OOD degradation versus 1142% for neural baselines under policy-induced shift; (2) 100% bootstrap CI coverage across 27 synthetic counterfactual experiments; and (3) Treatment Effect Accuracy exceeding 0.85. These results establish SL-BiLEM as an interpretable tool for public health decision-makers seeking accurate prediction and principled intervention planning.

Clinical decision-making is a feedback system where risk estimates influence treatment, which in turn changes disease trajectories, and both shape clinicians' measurement practices. Static prediction often fails clinically: models trained on observational care logs conflate disease biology with clinician behavior, particularly under treatment confounder feedback and irregular or informative observation. This Review focuses on intervention-aware disease trajectory modeling in clinical AI--methods estimating patient-specific longitudinal disease evolution and assessing trajectory changes under alternative treatments. We organize the field around six linked components: three decision tasks (factual forecasting, counterfactual estimation, policy evaluation) and three data-generating mechanisms (disease evolution, treatment assignment, observation process) that determine identifiability. We present the first unified framework bridging forecasting, counterfactual trajectories, and policy evaluation across discrete/continuous time, explicitly addressing treatment assignment, time-varying confounding, and observation bias. We synthesize key method families (multistate/joint models, temporal point-process, deep sequence architectures, longitudinal causal inference), map them to relevant components, and align evaluation with claim strength via overlap diagnostics, uncertainty quantification, off-policy robustness, and target-trial validation. This synthesis advances benchmark prediction to decision-grade clinical evidence, enabling treatment-sensitive individualized futures, pre-deployment policy stress-testing, and safer closed-loop learning health systems that adapt/abstain when evidence is insufficient.

Time series forecasting has become increasingly critical in real-world scenarios, where future sequences are influenced not only by historical patterns but also by forthcoming events. In this context, forecasting must dynamically adapt to complex and stochastic future conditions, which introduces fundamental challenges in both forecasting and evaluation. Traditional methods typically rely on historical data or factual future conditions, while overlooking counterfactual scenarios. Furthermore, many existing approaches are restricted to simple structured conditions, limiting their ability to generalize to the real-world complexities. To address these gaps, we introduce the task of counterfactual time series forecasting with textual conditions, enabling more flexible and condition-aware forecasting. We propose a comprehensive evaluation framework that encompasses both factual and counterfactual settings, even in the absence of ground truth time series. Additionally, we present a novel text-attribution mechanism that distinguishes mutable from immutable factors, thereby improving forecast accuracy under sophisticated and stochastic textual conditions. The project page is at https://seqml.github.io/TADiff/

In routine care, individuals identified a priori as high-risk are usually tested for conditions more frequently. Protected attributes, such as sex or ethnicity may also determine testing frequency. Such heterogeneous detection rates across a population induce label error. This causes systematic model error for specific groups and biases performance metrics during validation. This paper proposes a method to correct for such bias in prediction models due to differential diagnostic delay. We use a causal inference framework to define our target estimand: an individual's diagnosis probability in a counterfactual scenario where their diagnosis rate matches that of a reference group. We model the longitudinal process as a hidden Markov model, in which confirmatory test results are emissions from a latent progressive disease stage. We validate our approach in simulated data and apply it to a case study of chronic kidney disease prediction using electronic health records. In simulations, our method reduces prediction bias and improves calibration-in-the-large, correcting the Observed:Expected ratio in the underdiagnosed group from 1.34 (standard deviation: 0.09) in a model developed without any correction for underdiagnosis bias to 1.02 (0.09). Violations of assumptions in the simulation affected the estimation of model parameters, but the proposed approach nonetheless remained better calibrated than the standard model. In the clinical case study, we identify diabetes as the main driver of observability, with an odds ratio of 10.36 (95% confidence interval, 9.80 - 11.02) in 6-month urine albumin-creatinine ratio testing rate. Using our approach to predict the counterfactual diagnostic rate in patients without diabetes, we improved the Observed:Expected ratio of a developed clinical prediction model from 1.55 (1.51 - 1.59) to 1.01 (0.98 - 1.04).

Estimating individualized treatment effects from longitudinal observational data is central to data-driven medicine, yet existing methods face a fundamental limitation: reducing confounding bias often suppresses clinically informative heterogeneity, degrading patient-specific predictions. Here, we identify this tension as a bias-precision paradox in causal representation learning and introduce sampling-based maximum mean discrepancy (sMMD), a stochastic alignment strategy that replaces global adversarial balancing with subset-level matching. We instantiate this approach in a framework for counterfactual outcome prediction with attribution-grounded interpretability. Across two large-scale ICU cohorts (n = 27,783), our framework improves accuracy under distribution shift, reducing error by up to 11.5% and substantially increasing recall in high-risk tasks. Mechanistic analyses show that sMMD selectively preserves clinically decisive variables. In human-AI evaluation, our method outperforms clinicians-in-training and large language models, and improves clinician accuracy by 14.7% while reducing decision time, enabling interpretable, real-time clinical decision support.

Structural causal models provide a unified semantics for interventions and counterfactuals, but most identifiability results rely on restrictive assumptions like global monotonicity, which are often violated in embodied interaction, where the same exogenous perturbation can induce opposite responses under different contact contexts. We ask what structure still suffices once global monotonicity is dropped. We introduce non-monotone triangular structural causal models (NM-TM-SCM), which retain triangular recursion but replace global monotonicity with mechanism-wise invertibility and context-independent inverse transport. We prove that these conditions are equivalent to exogenous isomorphism and imply complete counterfactual identifiability, and we give a counterexample showing that local invertibility alone is insufficient. We instantiate the theory in CausalInverter, with triangular invertible layers, orientation gates, and transport-stability regularization. On synthetic non-monotonic mechanisms, the structural bias yields systematic counterfactual gains as non-monotonicity increases. On MuJoCo Door, our model achieves perfect event-level counterfactual recovery, lowers continuous angle error relative to a Transformer baseline, and delivers substantially more stable recovery than Transformer and conditional-flow predictors. On MuJoCo Push, where non-monotonicity is weaker, the same low-data predictors remain competitive or better, consistent with a bias-variance boundary. These results identify a broader identifiable regime between globally monotone triangular models and unconstrained black-box world models.

Clinical time-series forecasting is increasingly studied for decision support, yet standard aggregate metrics can obscure whether a model is actually useful for the task it is meant to serve. In safety-critical settings, low average error can coexist with dangerous failures in exactly the high-risk regimes that matter most. We present a task-aware evaluation framework for blood glucose forecasting built around two downstream uses: hypoglycemia early warning and insulin dosing decision support. For early warning, we evaluate on real data from three clinical cohorts using event-level recall and false alarms per patient-day, metrics that reflect operational alarm burden rather than aggregate accuracy. We show that models appearing acceptable overall, with recall above 0.9 on the full test set, can fail badly in the post-bolus slice, where insulin-on-board is elevated and missed warnings carry the greatest clinical consequences. Standard forecasting evaluation, however, does not test whether a model can reason about the effects of actions, a requirement for supporting insulin dosing decisions. We therefore add a second, interventional arm using the FDA-accepted UVA/Padova simulator, where we evaluate whether forecasters can predict glucose responses to altered insulin plans in paired factual/counterfactual scenarios. We show that models that look strong on real-data forecasting often fail to predict the direction, magnitude, or ranking of intervention effects, and choose poor insulin doses when evaluated under a clinically motivated cost. Taken together, the two arms reveal a consistent gap between forecasting accuracy and task-relevant usefulness. We release the benchmark, the standardized preprocessing pipeline for public cohorts, and the simulator-based interventional dataset as a reproducible toolkit.

Single-arm trials accelerate study timelines by reducing the number of patients that must be recruited for a concurrent control group. However, these designs require an alternative comparator to estimate treatment effects. One approach is to construct a virtual control arm using a machine learning (ML) model trained on external control data to predict the counterfactual outcomes of the treatment arm. Our aim in this study was to leverage virtual controls by developing and evaluating ML-based counterfactual outcome models trained on IFX-treated patients to predict 1-year steroid-free clinical remission (SFCR ) and a composite of C-reactive protein remission plus steroid-free clinical remission (CRP-SFCR) for ADA-treated pediatric Crohn's disease patients, and to compare the resulting IFX-versus-ADA treatment effect estimates with those obtained using propensity score matching to external controls. Five ML models were used to train counterfactual models on the observed IFX cohort data. The resulting models were used to predict the counterfactual outcomes for the ADA arm patients. LGBM yields the best OR closest to the propensity score matched reference, and all 95% CI results align with the conclusion from the reference study that no statistical difference in the primary and secondary outcomes has been observed between the patients treated with ADA or IFX. Our study supports virtual controls as a viable and effective substitute for expensive, lengthy or unethical patient recruitment in an inflammatory bowel disease (IBD) trial. The developed gradient boosted prediction model can be used as a pretrained model to generate IFX counterfactual predictions in future studies, pending external validation and assessment of transportability.

Baseline estimation is critical to Demand Response (DR) settlement in electricity markets, yet existing machine learning methods remain limited in predictive performance, while methodologies from causal inference and counterfactual prediction are still underutilized in this domain. We introduce a Generalized Synthetic Control Method that builds on the classical Synthetic Control Method (SCM) from econometrics. While SCM provides a powerful framework for counterfactual estimation, classical SCM remains a static estimator: it fits the treated unit as a combination of contemporaneous donor units and therefore ignores predictable temporal structure in the residual error. We develop a generalized SCM framework that transforms baseline estimation into a dynamic counterfactual prediction problem by augmenting the donor representation with exogenous features, lagged treated load, and selected lagged donor signals. This enriched representation allows the estimator to capture autoregressive dependence, delayed donor-response patterns, and error-correction effects beyond the scope of standard SCM. The framework further accommodates nonlinear predictors when linear weighting is inadequate, with the greatest benefit arising in limited-data settings. Experiments on the Ausgrid smart-meter dataset show consistent improvements over classical SCM and strong benchmark methods, with the dominant performance gains driven by dynamic augmentation.

The contemporary paradigm of trajectory learning operates fundamentally at the level of group dynamics, systematically reducing individual-level complexity to fit group-level models, thus rendering effective patient subtyping difficult and individual-level modeling largely out of reach. We propose a data-driven paradigm that introduces a dedicated individual-level temporal variable to capture \emph{Timing Attention} (i.e., the degree of concentration of an event's timing distribution across the patient cohort), thereby rendering timing a \emph{computable dimension} that enables individualized temporal features in trajectory learning. Instantiated as the Level-of-Individual Time Transformation (LITT) and applied to longitudinal EHR data from 3,276 breast cancer patients, the proposed paradigm demonstrates, for the first time to our knowledge: (1) automatic discovery of clinically significant patient trajectories, and (2) counterfactual timing deduction, that is, a \emph{What-If Machine}. Both results are purely data-driven, requiring no prior domain knowledge. LITT further achieves strong performance on timing prediction and survival analysis tasks.