Meng Hu

Yiwen Shi, Ping Ren, Jing Wang et al.

Food effect summarization from New Drug Application (NDA) is an essential component of product-specific guidance (PSG) development and assessment. However, manual summarization of food effect from extensive drug application review documents is time-consuming, which arouses a need to develop automated methods. Recent advances in large language models (LLMs) such as ChatGPT and GPT-4, have demonstrated great potential in improving the effectiveness of automated text summarization, but its ability regarding the accuracy in summarizing food effect for PSG assessment remains unclear. In this study, we introduce a simple yet effective approach, iterative prompting, which allows one to interact with ChatGPT or GPT-4 more effectively and efficiently through multi-turn interaction. Specifically, we propose a three-turn iterative prompting approach to food effect summarization in which the keyword-focused and length-controlled prompts are respectively provided in consecutive turns to refine the quality of the generated summary. We conduct a series of extensive evaluations, ranging from automated metrics to FDA professionals and even evaluation by GPT-4, on 100 NDA review documents selected over the past five years. We observe that the summary quality is progressively improved throughout the process. Moreover, we find that GPT-4 performs better than ChatGPT, as evaluated by FDA professionals (43% vs. 12%) and GPT-4 (64% vs. 35%). Importantly, all the FDA professionals unanimously rated that 85% of the summaries generated by GPT-4 are factually consistent with the golden reference summary, a finding further supported by GPT-4 rating of 72% consistency. These results strongly suggest a great potential for GPT-4 to draft food effect summaries that could be reviewed by FDA professionals, thereby improving the efficiency of PSG assessment cycle and promoting the generic drug product development.

Yiwen Shi, Jing Wang, Ping Ren et al.

Product-specific guidances (PSGs) recommended by the United States Food and Drug Administration (FDA) are instrumental to promote and guide generic drug product development. To assess a PSG, the FDA assessor needs to take extensive time and effort to manually retrieve supportive drug information of absorption, distribution, metabolism, and excretion (ADME) from the reference listed drug labeling. In this work, we leveraged the state-of-the-art pre-trained language models to automatically label the ADME paragraphs in the pharmacokinetics section from the FDA-approved drug labeling to facilitate PSG assessment. We applied a transfer learning approach by fine-tuning the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model to develop a novel application of ADME semantic labeling, which can automatically retrieve ADME paragraphs from drug labeling instead of manual work. We demonstrated that fine-tuning the pre-trained BERT model can outperform the conventional machine learning techniques, achieving up to 11.6% absolute F1 improvement. To our knowledge, we were the first to successfully apply BERT to solve the ADME semantic labeling task. We further assessed the relative contribution of pre-training and fine-tuning to the overall performance of the BERT model in the ADME semantic labeling task using a series of analysis methods such as attention similarity and layer-based ablations. Our analysis revealed that the information learned via fine-tuning is focused on task-specific knowledge in the top layers of the BERT, whereas the benefit from the pre-trained BERT model is from the bottom layers.

Taha ValizadehAslani, Yiwen Shi, Jing Wang et al.

Classification on long-tailed distributed data is a challenging problem, which suffers from serious class-imbalance and hence poor performance on tail classes with only a few samples. Owing to this paucity of samples, learning on the tail classes is especially challenging for the fine-tuning when transferring a pretrained model to a downstream task. In this work, we present a simple modification of standard fine-tuning to cope with these challenges. Specifically, we propose a two-stage fine-tuning: we first fine-tune the final layer of the pretrained model with class-balanced reweighting loss, and then we perform the standard fine-tuning. Our modification has several benefits: (1) it leverages pretrained representations by only fine-tuning a small portion of the model parameters while keeping the rest untouched; (2) it allows the model to learn an initial representation of the specific task; and importantly (3) it protects the learning of tail classes from being at a disadvantage during the model updating. We conduct extensive experiments on synthetic datasets of both two-class and multi-class tasks of text classification as well as a real-world application to ADME (i.e., absorption, distribution, metabolism, and excretion) semantic labeling. The experimental results show that the proposed two-stage fine-tuning outperforms both fine-tuning with conventional loss and fine-tuning with a reweighting loss on the above datasets.

Betty Xiong, Jillian Fisher, Benjamin Newman et al. · uw

We introduce an expert curated, real-world benchmark for evaluating document-grounded question-answering (QA) motivated by generic drug assessment, using the U.S. Food and Drug Administration (FDA) drug label documents. Drug labels contain rich but heterogeneous clinical and regulatory information, making accurate question answering difficult for current language models. In collaboration with FDA regulatory assessors, we introduce FDARxBench, and construct a multi-stage pipeline for generating high-quality, expert curated, QA examples spanning factual, multi-hop, and refusal tasks, and design evaluation protocols to assess both open-book and closed-book reasoning. Experiments across proprietary and open-weight models reveal substantial gaps in factual grounding, long-context retrieval, and safe refusal behavior. While motivated by FDA generic drug assessment needs, this benchmark also provides a substantial foundation for challenging regulatory-grade evaluation of label comprehension. The benchmark is designed to support evaluation of LLM behavior on drug-label questions.

Zilong Bai, Ruiji Zhang, Linqing Chen et al.

In recent years, large language models(LLMs) have attracted significant attention due to their exceptional performance across a multitude of natural language process tasks, and have been widely applied in various fields. However, the application of large language models in the Intellectual Property (IP) domain is challenging due to the strong need for specialized knowledge, privacy protection, processing of extremely long text in this field. In this technical report, we present for the first time a low-cost, standardized procedure for training IP-oriented LLMs, meeting the unique requirements of the IP domain. Using this standard process, we have trained the PatentGPT series models based on open-source pretrained models. By evaluating them on the open-source IP-oriented benchmark MOZIP, our domain-specific LLMs outperforms GPT-4, indicating the effectiveness of the proposed training procedure and the expertise of the PatentGPT models in the IP domain. Remarkably, our model surpassed GPT-4 on the 2019 China Patent Agent Qualification Examination, scoring 65 and matching human expert levels. Additionally, the PatentGPT model, which utilizes the SMoE architecture, achieves performance comparable to that of GPT-4 in the IP domain and demonstrates a better cost-performance ratio on long-text tasks, potentially serving as an alternative to GPT-4 within the IP domain.

Linqing Chen, Weilei Wang, Yubin Xia et al.

In this paper, we propose a novel system that integrates state-of-the-art, domain-specific large language models with advanced information retrieval techniques to deliver comprehensive and context-aware responses. Our approach facilitates seamless interaction among diverse components, enabling cross-validation of outputs to produce accurate, high-quality responses enriched with relevant data, images, tables, and other modalities. We demonstrate the system's capability to enhance response precision by leveraging a robust question-answering model, significantly improving the quality of dialogue generation. The system provides an accessible platform for real-time, high-fidelity interactions, allowing users to benefit from efficient human-computer interaction, precise retrieval, and simultaneous access to a wide range of literature and data. This dramatically improves the research efficiency of professionals in the biomedical and pharmaceutical domains and facilitates faster, more informed decision-making throughout the R\&D process. Furthermore, the system proposed in this paper is available at https://synapse-chat.patsnap.com.

Ran Wang, Xinlei Zhou, Meng Hu et al.

Despite the remarkable success of deep neural networks (DNNs), the security threat of adversarial attacks poses a significant challenge to the reliability of DNNs. In this paper, both theoretically and empirically, we discover a universal phenomenon that has been neglected in previous works, i.e., adversarial attacks tend to shift the distributions of feature statistics. Motivated by this finding, and by leveraging the advantages of uncertainty-aware stochastic methods in building robust models efficiently, we propose an uncertainty-driven feature statistics adjustment module for robustness enhancement, named Feature Statistics with Uncertainty (FSU). It randomly resamples channel-wise feature means and standard deviations of examples from multivariate Gaussian distributions, which helps to reconstruct the perturbed examples and calibrate the shifted distributions. The calibration recovers some domain characteristics of the data for classification, thereby mitigating the influence of perturbations and weakening the ability of attacks to deceive models. The proposed FSU module has universal applicability in training, attacking, predicting, and fine-tuning, demonstrating impressive robustness enhancement ability at a trivial additional time cost. For example, by fine-tuning the well-established models with FSU, the state-of-the-art methods achieve up to 17.13% and 34.82% robustness improvement against powerful AA and CW attacks on benchmark datasets.

Linqing Chen, Weilei Wang, Zilong Bai et al.

Large language models (LLMs) have revolutionized Natural Language Processing (NLP) by minimizing the need for complex feature engineering. However, the application of LLMs in specialized domains like biopharmaceuticals and chemistry remains largely unexplored. These fields are characterized by intricate terminologies, specialized knowledge, and a high demand for precision areas where general purpose LLMs often fall short. In this study, we introduce PharmaGPT, a suite of domain specilized LLMs with 13 billion and 70 billion parameters, specifically trained on a comprehensive corpus tailored to the Bio-Pharmaceutical and Chemical domains. Our evaluation shows that PharmaGPT surpasses existing general models on specific-domain benchmarks such as NAPLEX, demonstrating its exceptional capability in domain-specific tasks. Remarkably, this performance is achieved with a model that has only a fraction, sometimes just one-tenth-of the parameters of general-purpose large models. This advancement establishes a new benchmark for LLMs in the bio-pharmaceutical and chemical fields, addressing the existing gap in specialized language modeling. It also suggests a promising path for enhanced research and development, paving the way for more precise and effective NLP applications in these areas.