How well do LLMs cite relevant medical references? An evaluation framework and analyses

Large language models (LLMs) are currently being used to answer medical questions across a variety of clinical domains. Recent top-performing commercial LLMs, in particular, are also capable of citing sources to support their responses. In this paper, we ask: do the sources that LLMs generate actually support the claims that they make? To answer this, we propose three contributions. First, as expert medical annotations are an expensive and time-consuming bottleneck for scalable evaluation, we demonstrate that GPT-4 is highly accurate in validating source relevance, agreeing 88% of the time with a panel of medical doctors. Second, we develop an end-to-end, automated pipeline called \textit{SourceCheckup} and use it to evaluate five top-performing LLMs on a dataset of 1200 generated questions, totaling over 40K pairs of statements and sources. Interestingly, we find that between ~50% to 90% of LLM responses are not fully supported by the sources they provide. We also evaluate GPT-4 with retrieval augmented generation (RAG) and find that, even still, around 30\% of individual statements are unsupported, while nearly half of its responses are not fully supported. Third, we open-source our curated dataset of medical questions and expert annotations for future evaluations. Given the rapid pace of LLM development and the potential harms of incorrect or outdated medical information, it is crucial to also understand and quantify their capability to produce relevant, trustworthy medical references.

DataInf: Efficiently Estimating Data Influence in LoRA-tuned LLMs and Diffusion Models

Quantifying the impact of training data points is crucial for understanding the outputs of machine learning models and for improving the transparency of the AI pipeline. The influence function is a principled and popular data attribution method, but its computational cost often makes it challenging to use. This issue becomes more pronounced in the setting of large language models and text-to-image models. In this work, we propose DataInf, an efficient influence approximation method that is practical for large-scale generative AI models. Leveraging an easy-to-compute closed-form expression, DataInf outperforms existing influence computation algorithms in terms of computational and memory efficiency. Our theoretical analysis shows that DataInf is particularly well-suited for parameter-efficient fine-tuning techniques such as LoRA. Through systematic empirical evaluations, we show that DataInf accurately approximates influence scores and is orders of magnitude faster than existing methods. In applications to RoBERTa-large, Llama-2-13B-chat, and stable-diffusion-v1.5 models, DataInf effectively identifies the most influential fine-tuning examples better than other approximate influence scores. Moreover, it can help to identify which data points are mislabeled.

Explaining medical AI performance disparities across sites with confounder Shapley value analysis

Medical AI algorithms can often experience degraded performance when evaluated on previously unseen sites. Addressing cross-site performance disparities is key to ensuring that AI is equitable and effective when deployed on diverse patient populations. Multi-site evaluations are key to diagnosing such disparities as they can test algorithms across a broader range of potential biases such as patient demographics, equipment types, and technical parameters. However, such tests do not explain why the model performs worse. Our framework provides a method for quantifying the marginal and cumulative effect of each type of bias on the overall performance difference when a model is evaluated on external data. We demonstrate its usefulness in a case study of a deep learning model trained to detect the presence of pneumothorax, where our framework can help explain up to 60% of the discrepancy in performance across different sites with known biases like disease comorbidities and imaging parameters.

Synthesizing lesions using contextual GANs improves breast cancer classification on mammograms

Data scarcity and class imbalance are two fundamental challenges in many machine learning applications to healthcare. Breast cancer classification in mammography exemplifies these challenges, with a malignancy rate of around 0.5% in a screening population, which is compounded by the relatively small size of lesions (~1% of the image) in malignant cases. Simultaneously, the prevalence of screening mammography creates a potential abundance of non-cancer exams to use for training. Altogether, these characteristics lead to overfitting on cancer cases, while under-utilizing non-cancer data. Here, we present a novel generative adversarial network (GAN) model for data augmentation that can realistically synthesize and remove lesions on mammograms. With self-attention and semi-supervised learning components, the U-net-based architecture can generate high resolution (256x256px) outputs, as necessary for mammography. When augmenting the original training set with the GAN-generated samples, we find a significant improvement in malignancy classification performance on a test set of real mammogram patches. Overall, the empirical results of our algorithm and the relevance to other medical imaging paradigms point to potentially fruitful further applications.

Robust breast cancer detection in mammography and digital breast tomosynthesis using annotation-efficient deep learning approach

Breast cancer remains a global challenge, causing over 1 million deaths globally in 2018. To achieve earlier breast cancer detection, screening x-ray mammography is recommended by health organizations worldwide and has been estimated to decrease breast cancer mortality by 20-40%. Nevertheless, significant false positive and false negative rates, as well as high interpretation costs, leave opportunities for improving quality and access. To address these limitations, there has been much recent interest in applying deep learning to mammography; however, obtaining large amounts of annotated data poses a challenge for training deep learning models for this purpose, as does ensuring generalization beyond the populations represented in the training dataset. Here, we present an annotation-efficient deep learning approach that 1) achieves state-of-the-art performance in mammogram classification, 2) successfully extends to digital breast tomosynthesis (DBT; "3D mammography"), 3) detects cancers in clinically-negative prior mammograms of cancer patients, 4) generalizes well to a population with low screening rates, and 5) outperforms five-out-of-five full-time breast imaging specialists by improving absolute sensitivity by an average of 14%. Our results demonstrate promise towards software that can improve the accuracy of and access to screening mammography worldwide.

Validation of a deep learning mammography model in a population with low screening rates

A key promise of AI applications in healthcare is in increasing access to quality medical care in under-served populations and emerging markets. However, deep learning models are often only trained on data from advantaged populations that have the infrastructure and resources required for large-scale data collection. In this paper, we aim to empirically investigate the potential impact of such biases on breast cancer detection in mammograms. We specifically explore how a deep learning algorithm trained on screening mammograms from the US and UK generalizes to mammograms collected at a hospital in China, where screening is not widely implemented. For the evaluation, we use a top-scoring model developed for the Digital Mammography DREAM Challenge. Despite the change in institution and population composition, we find that the model generalizes well, exhibiting similar performance to that achieved in the DREAM Challenge, even when controlling for tumor size. We also illustrate a simple but effective method for filtering predictions based on model variance, which can be particularly useful for deployment in new settings. While there are many components in developing a clinically effective system, these results represent a promising step towards increasing access to life-saving screening mammography in populations where screening rates are currently low.

Mixed Membership Recurrent Neural Networks

Models for sequential data such as the recurrent neural network (RNN) often implicitly model a sequence as having a fixed time interval between observations and do not account for group-level effects when multiple sequences are observed. We propose a model for grouped sequential data based on the RNN that accounts for varying time intervals between observations in a sequence by learning a group-level base parameter to which each sequence can revert. Our approach is motivated by the mixed membership framework, and we show how it can be used for dynamic topic modeling in which the distribution on topics (not the topics themselves) are evolving in time. We demonstrate our approach on a dataset of 3.4 million online grocery shopping orders made by 206K customers.

Conditional Infilling GANs for Data Augmentation in Mammogram Classification

Deep learning approaches to breast cancer detection in mammograms have recently shown promising results. However, such models are constrained by the limited size of publicly available mammography datasets, in large part due to privacy concerns and the high cost of generating expert annotations. Limited dataset size is further exacerbated by substantial class imbalance since "normal" images dramatically outnumber those with findings. Given the rapid progress of generative models in synthesizing realistic images, and the known effectiveness of simple data augmentation techniques (e.g. horizontal flipping), we ask if it is possible to synthetically augment mammogram datasets using generative adversarial networks (GANs). We train a class-conditional GAN to perform contextual in-filling, which we then use to synthesize lesions onto healthy screening mammograms. First, we show that GANs are capable of generating high-resolution synthetic mammogram patches. Next, we experimentally evaluate using the augmented dataset to improve breast cancer classification performance. We observe that a ResNet-50 classifier trained with GAN-augmented training data produces a higher AUROC compared to the same model trained only on traditionally augmented data, demonstrating the potential of our approach.

Learning Scene Gist with Convolutional Neural Networks to Improve Object Recognition

Advancements in convolutional neural networks (CNNs) have made significant strides toward achieving high performance levels on multiple object recognition tasks. While some approaches utilize information from the entire scene to propose regions of interest, the task of interpreting a particular region or object is still performed independently of other objects and features in the image. Here we demonstrate that a scene's 'gist' can significantly contribute to how well humans can recognize objects. These findings are consistent with the notion that humans foveate on an object and incorporate information from the periphery to aid in recognition. We use a biologically inspired two-part convolutional neural network ('GistNet') that models the fovea and periphery to provide a proof-of-principle demonstration that computational object recognition can significantly benefit from the gist of the scene as contextual information. Our model yields accuracy improvements of up to 50% in certain object categories when incorporating contextual gist, while only increasing the original model size by 5%. This proposed model mirrors our intuition about how the human visual system recognizes objects, suggesting specific biologically plausible constraints to improve machine vision and building initial steps towards the challenge of scene understanding.