搜索结果：Contemporary clinical trials communications

In the context of clinical research, computational models have received increasing attention over the past decades. In this systematic review, we aimed to provide an overview of the role of so-called in silico clinical trials (ISCTs) in medical applications. Exemplary for the broad field of clinical medicine, we focused on in silico (IS) methods applied in drug development, sometimes also referred to as model informed drug development (MIDD). We searched PubMed and ClinicalTrials.gov for published articles and registered clinical trials related to ISCTs. We identified 202 articles and 48 trials, and of these, 76 articles and 19 trials were directly linked to drug development. We extracted information from all 202 articles and 48 clinical trials and conducted a more detailed review of the methods used in the 76 articles that are connected to drug development. Regarding application, most articles and trials focused on cancer and imaging-related research while rare and pediatric diseases were only addressed in 14 articles and 5 trials, respectively. While some models were informed combining mechanistic knowledge with clinical or preclinical (in-vivo or in-vitro) data, the majority of

Analyzing data from past clinical trials is part of the ongoing effort to optimize the design, implementation, and execution of new clinical trials and more efficiently bring life-saving interventions to market. While there have been recent advances in the generation of static context synthetic clinical trial data, due to both limited patient availability and constraints imposed by patient privacy needs, the generation of fine-grained synthetic time-sequential clinical trial data has been challenging. Given that patient trajectories over an entire clinical trial are of high importance for optimizing trial design and efforts to prevent harmful adverse events, there is a significant need for the generation of high-fidelity time-sequence clinical trial data. Here we introduce TrialSynth, a Variational Autoencoder (VAE) designed to address the specific challenges of generating synthetic time-sequence clinical trial data. Distinct from related clinical data VAE methods, the core of our method leverages Hawkes Processes (HP), which are particularly well-suited for modeling event-type and time gap prediction needed to capture the structure of sequential clinical trial data. Our experiment

Clinical trials are an indispensable part of the drug development process, bridging the gap between basic research and clinical application. During the development of new drugs, clinical trials are used not only to evaluate the safety and efficacy of the drug but also to explore its dosage, treatment regimens, and potential side effects. This review discusses the various stages of clinical trials, including Phase I (safety assessment), Phase II (preliminary efficacy evaluation), Phase III (large-scale validation), and Phase IV (post-marketing surveillance), highlighting the characteristics of each phase and their interrelationships. Additionally, the paper addresses the major challenges encountered in clinical trials, such as ethical issues, subject recruitment difficulties, diversity and representativeness concerns, and proposes strategies for overcoming these challenges. With the advancement of technology, innovative technologies such as artificial intelligence, big data, and digitalization are gradually transforming clinical trial design and implementation, improving trial efficiency and data quality. The article also looks forward to the future of clinical trials, particularly

Clinical trials shape medical evidence and determine who gains access to experimental therapies. Whether participation in these trials reflects the global burden of disease remains unclear. Here we analyze participation inequality across more than 62,000 randomized controlled trials spanning 16 major disease categories from 2000 to 2024. Linking 36.8 million trial participants to country-level disease burden, we show that global inequality in clinical trials participation is overwhelmingly shaped by country rather than disease burden. Country-level factors explain over 90% of variation in participation, whereas disease-specific effects contribute only marginally. Removing entire disease categories-including those traditionally considered underfunded-has little effect on overall inequality. Instead, participation is highly concentrated geographically, with a small group of countries enrolling a disproportionate share of participants across nearly all diseases. These patterns have persisted despite decades of disease-targeted funding and increasing alignment between research attention and disease burden within diseases. Our findings indicate that disease-vertical strategies alone can

Clinical trials assessing neurological treatment are challenging due to the diversity of brain function, and the difficulty in quantifying it. Traditional treatment studies in epilepsy use seizure frequency as the primary outcome measure, which may overlooking meaningful improvements in patients' quality of life. This paper introduces the Clinical Instrument for Measuring Patient Anecdotes in Clinical Trials (Clinical IMPACT), a novel tool designed to capture qualitative non-seizure improvement across neurological domains. The Clinical IMPACT incorporates open-ended inquiries that allow participants or caregivers to identify and select anecdotal evidence of their most significant treatment benefits. A blinded panel of experts ranks these anecdotes, facilitating a rigorous statistical analysis using the Wilcoxon Rank-Sum Test to detect treatment efficacy. The approach is resistant to type 1 error, yet comprehensive in its ability to capture real-world effects on quality of life. The potential of the Clinical IMPACT tool to enhance sensitivity while also providing qualitative insights that can inform patients, healthcare providers, and regulatory bodies about treatment effects makes

Dynamic treatment regimes have been proposed to personalize treatment decisions by utilizing historical patient data, but they may not always improve on the current standard of care. It is thus meaningful to integrate the standard of care into the evaluation of treatment strategies, and previous works have suggested doing so through the concept of clinical utility. Here we will focus on the comparative component of clinical utility as the average outcome had the full population received treatment based on the proposed dynamic treatment regime in comparison to the full population receiving the ``standard" treatment assignment mechanism, such as a physician's choice. Clinical trials to evaluate clinical utility are rarely conducted, and thus, previous works have proposed an emulated clinical trial framework using observational data. However, only one simple estimator was previously suggested, and the practical details of how one would conduct this emulated trial were not detailed. Here, we illuminate these details and propose several estimators of clinical utility based on estimators proposed in the dynamic treatment regime literature. We illustrate the considerations and the estimat

In the design of clinical trials, it is essential to assess the design operating characteristics (e.g., power and the type I error rate). Common practice for the evaluation of operating characteristics in Bayesian clinical trials relies on estimating the sampling distribution of posterior summaries via Monte Carlo simulation. It is computationally intensive to repeat this estimation process for each design configuration considered, particularly for clustered data that are analyzed using complex, high-dimensional models. In this paper, we propose an efficient method to assess operating characteristics and determine sample sizes for Bayesian trials with clustered data. We prove theoretical results that enable posterior probabilities to be modeled as a function of the number of clusters. Using these functions, we assess operating characteristics at a range of sample sizes given simulations conducted at only two cluster counts. These theoretical results are also leveraged to quantify the impact of simulation variability on our sample size recommendations. The applicability of our methodology is illustrated using an example cluster-randomized Bayesian clinical trial.

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

The competency of any intelligent agent is bounded by its formal account of the world in which it operates. Clinical AI lacks such an account. Existing frameworks address evaluation, regulation, or system design in isolation, without a shared model of the clinical world to connect them. We introduce the Clinical World Model, a framework that formalizes care as a tripartite interaction among Patient, Provider, and Ecosystem. To formalize how any agent, whether human or artificial, transforms information into clinical action, we develop parallel decision-making architectures for providers, patients, and AI agents, grounded in validated principles of clinical cognition. The Clinical AI Skill-Mix operationalizes competency through eight dimensions. Five define the clinical competency space (condition, phase, care setting, provider role, and task) and three specify how AI engages human reasoning (assigned authority, agent facing, and anchoring layer). The combinatorial product of these dimensions yields a space of billions of distinct competency coordinates. A central structural implication is that validation within one coordinate provides minimal evidence for performance in another, re

A clinical trial is an essential step in drug development, which is often costly and time-consuming. In silico trials are clinical trials conducted digitally through simulation and modeling as an alternative to traditional clinical trials. AI-enabled in silico trials can increase the case group size by creating virtual cohorts as controls. In addition, it also enables automation and optimization of trial design and predicts the trial success rate. This article systematically reviews papers under three main topics: clinical simulation, individualized predictive modeling, and computer-aided trial design. We focus on how machine learning (ML) may be applied in these applications. In particular, we present the machine learning problem formulation and available data sources for each task. We end with discussing the challenges and opportunities of AI for in silico trials in real-world applications.

Pragmatic clinical trials evaluate the effectiveness of health interventions in real-world settings. Negative spillover can arise in a pragmatic trial if the study intervention affects how scarce resources are allocated between patients in the intervention and comparison groups. This can harm patients assigned to the control group and lead to overestimation of treatment effect. While this type of negative spillover is often addressed in trials of social welfare and public health interventions, there is little recognition of this source of bias in the medical literature. In this article, I examine what causes negative spillover and how it may have led clinical trial investigators to overestimate the effect of patient navigation, AI-based physiological alarms, and elective induction of labor. I also suggest ways to detect negative spillover and design trials that avoid this potential source of bias.

Identifying cohorts of patients based on eligibility criteria such as medical conditions, procedures, and medication use is critical to recruitment for clinical trials. Such criteria are often most naturally described in free-text, using language familiar to clinicians and researchers. In order to identify potential participants at scale, these criteria must first be translated into queries on clinical databases, which can be labor-intensive and error-prone. Natural language processing (NLP) methods offer a potential means of such conversion into database queries automatically. However they must first be trained and evaluated using corpora which capture clinical trials criteria in sufficient detail. In this paper, we introduce the Leaf Clinical Trials (LCT) corpus, a human-annotated corpus of over 1,000 clinical trial eligibility criteria descriptions using highly granular structured labels capturing a range of biomedical phenomena. We provide details of our schema, annotation process, corpus quality, and statistics. Additionally, we present baseline information extraction results on this corpus as benchmarks for future work.

The clinical trial process, a critical phase in drug development, is essential for developing new treatments. The primary goal of interventional clinical trials is to evaluate the safety and efficacy of drug-based treatments for specific diseases. However, these trials are often lengthy, labor-intensive, and expensive. The duration of a clinical trial significantly impacts overall costs, making efficient timeline management crucial for controlling budgets and ensuring the economic feasibility of research. To address this issue, We propose TrialDura, a machine learning-based method that estimates the duration of clinical trials using multimodal data, including disease names, drug molecules, trial phases, and eligibility criteria. Then, we encode them into Bio-BERT embeddings specifically tuned for biomedical contexts to provide a deeper and more relevant semantic understanding of clinical trial data. Finally, the model's hierarchical attention mechanism connects all of the embeddings to capture their interactions and predict clinical trial duration. Our proposed model demonstrated superior performance with a mean absolute error (MAE) of 1.04 years and a root mean square error (RMSE)

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1,015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TrialGPT.

Bayesian adaptive designs have gained popularity in all phases of clinical trials with numerous new developments in the past few decades. During the COVID-19 pandemic, the need to establish evidence for the effectiveness of vaccines, therapeutic treatments and policies that could resolve or control the crisis emphasized the advantages offered by efficient and flexible clinical trial designs. In many COVID-19 clinical trials, due to the high level of uncertainty, Bayesian adaptive designs were considered advantageous. Designing Bayesian adaptive trials, however, requires extensive simulation studies that are generally considered challenging, particularly in time-sensitive settings such as a pandemic. In this article, we propose a set of methods for efficient estimation and uncertainty quantification for design operating characteristics of Bayesian adaptive trials. Specifically, we model the sampling distribution of Bayesian probability statements that are commonly used as the basis of decision making. To showcase the implementation and performance of the proposed approach, we use a clinical trial design with an ordinal disease-progression scale endpoint that was popular among COVID-

Clinical AI development has traditionally followed a collaborative paradigm that depends on close interaction between clinicians and specialized AI teams. This paradigm imposes a practical challenge: clinicians must repeatedly communicate and refine their requirements with AI developers before those requirements can be translated into executable model development. This iterative process is time-consuming, and even after repeated discussion, misalignment may still exist because the two sides do not fully share each other's expertise. However, autonomous coding agents may change this paradigm, raising the possibility that clinicians could develop clinical AI models independently through natural-language interaction alone. In this study, we present such an autonomous prototype for clinician-driven clinical AI development. We evaluated the system on five clinical tasks spanning dermoscopic lesion classification, melanoma-versus-nevus triage, wrist-fracture detection (including a weakly supervised variant with only 5% bounding-box annotations), and debiased pneumothorax classification on chest radiographs. Across these settings, the system consistently developed models from clinician re

This paper presents a novel approach to active learning that takes into account the non-independent and identically distributed (non-i.i.d.) structure of a clinical trial setting. There exists two types of clinical trials: retrospective and prospective. Retrospective clinical trials analyze data after treatment has been performed; prospective clinical trials collect data as treatment is ongoing. Typically, active learning approaches assume the dataset is i.i.d. when selecting training samples; however, in the case of clinical trials, treatment results in a dependency between the data collected at the current and past visits. Thus, we propose prospective active learning to overcome the limitations present in traditional active learning methods and apply it to disease detection in optical coherence tomography (OCT) images, where we condition on the time an image was collected to enforce the i.i.d. assumption. We compare our proposed method to the traditional active learning paradigm, which we refer to as retrospective in nature. We demonstrate that prospective active learning outperforms retrospective active learning in two different types of test settings.

Detecting duplicate patient participation in clinical trials is a major challenge because repeated patients can undermine the credibility and accuracy of the trial's findings and result in significant health and financial risks. Developing accurate automated speaker verification (ASV) models is crucial to verify the identity of enrolled individuals and remove duplicates, but the size and quality of data influence ASV performance. However, there has been limited investigation into the factors that can affect ASV capabilities in clinical environments. In this paper, we bridge the gap by conducting analysis of how participant demographic characteristics, audio quality criteria, and severity level of Alzheimer's disease (AD) impact the performance of ASV utilizing a dataset of speech recordings from 659 participants with varying levels of AD, obtained through multiple speech tasks. Our results indicate that ASV performance: 1) is slightly better on male speakers than on female speakers; 2) degrades for individuals who are above 70 years old; 3) is comparatively better for non-native English speakers than for native English speakers; 4) is negatively affected by clinician interference,

Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model named Panacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, named TrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curate TrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enable Panacea to be widely applicable for a range of clinical trial tasks based on user requirements. We evaluated Panacea on a new benchmark, named TrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-spec