Jan F. Nygård

Chengjie Lu, Qinghua Xu, Tao Yue et al.

The Cancer Registry of Norway (CRN) collects information on cancer patients by receiving cancer messages from different medical entities (e.g., medical labs, and hospitals) in Norway. Such messages are validated by an automated cancer registry system: GURI. Its correct operation is crucial since it lays the foundation for cancer research and provides critical cancer-related statistics to its stakeholders. Constructing a cyber-cyber digital twin (CCDT) for GURI can facilitate various experiments and advanced analyses of the operational state of GURI without requiring intensive interactions with the real system. However, GURI constantly evolves due to novel medical diagnostics and treatment, technological advances, etc. Accordingly, CCDT should evolve as well to synchronize with GURI. A key challenge of achieving such synchronization is that evolving CCDT needs abundant data labelled by the new GURI. To tackle this challenge, we propose EvoCLINICAL, which considers the CCDT developed for the previous version of GURI as the pretrained model and fine-tunes it with the dataset labelled by querying a new GURI version. EvoCLINICAL employs a genetic algorithm to select an optimal subset of cancer messages from a candidate dataset and query GURI with it. We evaluate EvoCLINICAL on three evolution processes. The precision, recall, and F1 score are all greater than 91%, demonstrating the effectiveness of EvoCLINICAL. Furthermore, we replace the active learning part of EvoCLINICAL with random selection to study the contribution of transfer learning to the overall performance of EvoCLINICAL. Results show that employing active learning in EvoCLINICAL increases its performances consistently.

Narasimha Raghavan Veeraragavan, Svetlana Boudko, Jan Franz Nygård

The proliferation of healthcare data has expanded opportunities for collaborative research, yet stringent privacy regulations hinder pooling sensitive patient records. We propose a \emph{multiparty homomorphic encryption-based} framework for \emph{privacy-preserving federated Kaplan--Meier survival analysis}, offering native floating-point support, a theoretical model, and explicit reconstruction-attack mitigation. Compared to prior work, our framework ensures encrypted federated survival estimates closely match centralized outcomes, supported by formal utility-loss bounds that demonstrate convergence as aggregation and decryption noise diminish. Extensive experiments on the NCCTG Lung Cancer and synthetic Breast Cancer datasets confirm low \emph{mean absolute error (MAE)} and \emph{root mean squared error (RMSE)}, indicating negligible deviations between encrypted and non-encrypted survival curves. Log-rank and numerical accuracy tests reveal \emph{no significant difference} between federated encrypted and non-encrypted analyses, preserving statistical validity. A reconstruction-attack evaluation shows smaller federations (2--3 providers) with overlapping data between the institutions are vulnerable, a challenge mitigated by multiparty encryption. Larger federations (5--50 sites) degrade reconstruction accuracy further, with encryption improving confidentiality. Despite an 8--19$\times$ computational overhead, threshold-based homomorphic encryption is \emph{feasible for moderate-scale deployments}, balancing security and runtime. By providing robust privacy guarantees alongside high-fidelity survival estimates, our framework advances the state-of-the art in secure multi-institutional survival analysis.

Erblin Isaku, Christoph Laaber, Hassan Sartaj et al.

The Cancer Registry of Norway (CRN) uses an automated cancer registration support system (CaReSS) to support core cancer registry activities, i.e, data capture, data curation, and producing data products and statistics for various stakeholders. GURI is a core component of CaReSS, which is responsible for validating incoming data with medical rules. Such medical rules are manually implemented by medical experts based on medical standards, regulations, and research. Since large language models (LLMs) have been trained on a large amount of public information, including these documents, they can be employed to generate tests for GURI. Thus, we propose an LLM-based test generation and differential testing approach (LLMeDiff) to test GURI. We experimented with four different LLMs, two medical rule engine implementations, and 58 real medical rules to investigate the hallucination, success, time efficiency, and robustness of the LLMs to generate tests, and these tests' ability to find potential issues in GURI. Our results showed that GPT-3.5 hallucinates the least, is the most successful, and is generally the most robust; however, it has the worst time efficiency. Our differential testing revealed 22 medical rules where implementation inconsistencies were discovered (e.g., regarding handling rule versions). Finally, we provide insights for practitioners and researchers based on the results.

Narasimha Raghavan Veeraragavan, Mohammad Hossein Tabatabaei, Severin Elvatun et al.

Synthetic data generation is increasingly recognized as a crucial solution to address data related challenges such as scarcity, bias, and privacy concerns. As synthetic data proliferates, the need for a robust evaluation framework to select a synthetic data generator becomes more pressing given the variety of options available. In this research study, we investigate two primary questions: 1) How can we select the most suitable synthetic data generator from a set of options for a specific purpose? 2) How can we make the selection process more transparent, accountable, and auditable? To address these questions, we introduce a novel approach in which the proposed ranking algorithm is implemented as a smart contract within a permissioned blockchain framework called Sawtooth. Through comprehensive experiments and comparisons with state-of-the-art baseline ranking solutions, our framework demonstrates its effectiveness in providing nuanced rankings that consider both desirable and undesirable properties. Furthermore, our framework serves as a valuable tool for selecting the optimal synthetic data generators for specific needs while ensuring compliance with data protection principles.

Narasimha Raghavan Veeraragavan, Sai Praneeth Karimireddy, Jan Franz Nygård

This paper presents a differentially private approach to Kaplan-Meier estimation that achieves accurate survival probability estimates while safeguarding individual privacy. The Kaplan-Meier estimator is widely used in survival analysis to estimate survival functions over time, yet applying it to sensitive datasets, such as clinical records, risks revealing private information. To address this, we introduce a novel algorithm that applies time-indexed Laplace noise, dynamic clipping, and smoothing to produce a privacy-preserving survival curve while maintaining the cumulative structure of the Kaplan-Meier estimator. By scaling noise over time, the algorithm accounts for decreasing sensitivity as fewer individuals remain at risk, while dynamic clipping and smoothing prevent extreme values and reduce fluctuations, preserving the natural shape of the survival curve. Our results, evaluated on the NCCTG lung cancer dataset, show that the proposed method effectively lowers root mean squared error (RMSE) and enhances accuracy across privacy budgets ($ε$). At $ε= 10$, the algorithm achieves an RMSE as low as 0.04, closely approximating non-private estimates. Additionally, membership inference attacks reveal that higher $ε$ values (e.g., $ε\geq 6$) significantly reduce influential points, particularly at higher thresholds, lowering susceptibility to inference attacks. These findings confirm that our approach balances privacy and utility, advancing privacy-preserving survival analysis.

Narasimha Raghavan Veeraragavan, Jan Franz Nygård

We investigate how to calculate Kaplan-Meier survival curves across multiple health-care jurisdictions while protecting patient privacy with node-level differential privacy. Each site discloses its curve only once, adding Laplace noise whose scale is determined by the length of the common time grid; the server then averages the noisy curves, so the overall privacy budget remains unchanged. We benchmark four one-shot smoothing techniques: Discrete Cosine Transform, Haar Wavelet shrinkage, adaptive Total-Variation denoising, and a parametric Weibull fit on the NCCTG lung-cancer cohort under five privacy levels and three partition scenarios (uniform, moderately skewed, highly imbalanced). Total-Variation gives the best mean accuracy, whereas the frequency-domain smoothers offer stronger worst-case robustness and the Weibull model shows the most stable behaviour at the strictest privacy setting. Across all methods the released curves keep the empirical log-rank type-I error below fifteen percent for privacy budgets of 0.5 and higher, demonstrating that clinically useful survival information can be shared without iterative training or heavy cryptography.

Narasimha Raghavan Veeraragavan, Jan Franz Nygård

We propose Guardian-FC, a novel two-layer framework for privacy preserving federated computing that unifies safety enforcement across diverse privacy preserving mechanisms, including cryptographic back-ends like fully homomorphic encryption (FHE) and multiparty computation (MPC), as well as statistical techniques such as differential privacy (DP). Guardian-FC decouples guard-rails from privacy mechanisms by executing plug-ins (modular computation units), written in a backend-neutral, domain-specific language (DSL) designed specifically for federated computing workflows and interchangeable Execution Providers (EPs), which implement DSL operations for various privacy back-ends. An Agentic-AI control plane enforces a finite-state safety loop through signed telemetry and commands, ensuring consistent risk management and auditability. The manifest-centric design supports fail-fast job admission and seamless extensibility to new privacy back-ends. We present qualitative scenarios illustrating backend-agnostic safety and a formal model foundation for verification. Finally, we outline a research agenda inviting the community to advance adaptive guard-rail tuning, multi-backend composition, DSL specification development, implementation, and compiler extensibility alongside human-override usability.

Vibeke Binz Vallevik, Serena Elizabeth Marshall, Aleksandar Babic et al.

Synthetic data is emerging as a cost-effective solution necessary to meet the increasing data demands of AI development, created either from existing knowledge or derived from real data. The traditional classification of synthetic data types into hybrid, partial or fully synthetic datasets has limited value and does not reflect the ever-increasing methods to generate synthetic data. The generation method and their source jointly shape the characteristics of synthetic data, which in turn determines its practical applications. We make a case for an alternative approach to grouping synthetic data types that better reflect privacy perspectives in order to facilitate regulatory guidance in the generation and processing of synthetic data. This approach to classification provides flexibility to new advancements like deep generative methods and offers a more practical framework for future applications.

Vibeke Binz Vallevik, Aleksandar Babic, Serena Elizabeth Marshall et al.

Ensuring safe adoption of AI tools in healthcare hinges on access to sufficient data for training, testing and validation. In response to privacy concerns and regulatory requirements, using synthetic data has been suggested. Synthetic data is created by training a generator on real data to produce a dataset with similar statistical properties. Competing metrics with differing taxonomies for quality evaluation have been suggested, resulting in a complex landscape. Optimising quality entails balancing considerations that make the data fit for use, yet relevant dimensions are left out of existing frameworks. We performed a comprehensive literature review on the use of quality evaluation metrics on SD within the scope of tabular healthcare data and SD made using deep generative methods. Based on this and the collective team experiences, we developed a conceptual framework for quality assurance. The applicability was benchmarked against a practical case from the Dutch National Cancer Registry. We present a conceptual framework for quality assurance of SD for AI applications in healthcare that aligns diverging taxonomies, expands on common quality dimensions to include the dimensions of Fairness and Carbon footprint, and proposes stages necessary to support real-life applications. Building trust in synthetic data by increasing transparency and reducing the safety risk will accelerate the development and uptake of trustworthy AI tools for the benefit of patients. Despite the growing emphasis on algorithmic fairness and carbon footprint, these metrics were scarce in the literature review. The overwhelming focus was on statistical similarity using distance metrics while sequential logic detection was scarce. A consensus-backed framework that includes all relevant quality dimensions can provide assurance for safe and responsible real-life applications of SD.

Rui Meng, Soper Braden, Jan Nygard et al.

Hidden Markov jump processes are an attractive approach for modeling clinical disease progression data because they are explainable and capable of handling both irregularly sampled and noisy data. Most applications in this context consider time-homogeneous models due to their relative computational simplicity. However, the time homogeneous assumption is too strong to accurately model the natural history of many diseases. Moreover, the population at risk is not homogeneous either, since disease exposure and susceptibility can vary considerably. In this paper, we propose a piece-wise stationary transition matrix to explain the heterogeneity in time. We propose a hierarchical structure for the heterogeneity in population, where prior information is considered to deal with unbalanced data. Moreover, an efficient, scalable EM algorithm is proposed for inference. We demonstrate the feasibility and superiority of our model on a cervical cancer screening dataset from the Cancer Registry of Norway. Experiments show that our model outperforms state-of-the-art recurrent neural network models in terms of prediction accuracy and significantly outperforms a standard hidden Markov jump process in generating Kaplan-Meier estimators.