Appraising the Potential Uses and Harms of LLMs for Medical Systematic Reviews

Medical systematic reviews are crucial for informing clinical decision making and healthcare policy. But producing such reviews is onerous and time-consuming. Thus, high-quality evidence synopses are not available for many questions and may be outdated even when they are available. Large language models (LLMs) are now capable of generating long-form texts, suggesting the tantalizing possibility of automatically generating literature reviews on demand. However, LLMs sometimes generate inaccurate (and potentially misleading) texts by hallucinating or omitting important information. In the healthcare context, this may render LLMs unusable at best and dangerous at worst. Most discussion surrounding the benefits and risks of LLMs have been divorced from specific applications. In this work, we seek to qualitatively characterize the potential utility and risks of LLMs for assisting in production of medical evidence reviews. We conducted 16 semi-structured interviews with international experts in systematic reviews, grounding discussion in the context of generating evidence reviews. Domain experts indicated that LLMs could aid writing reviews, as a tool for drafting or creating plain language summaries, generating templates or suggestions, distilling information, crosschecking, and synthesizing or interpreting text inputs. But they also identified issues with model outputs and expressed concerns about potential downstream harms of confidently composed but inaccurate LLM outputs which might mislead. Other anticipated potential downstream harms included lessened accountability and proliferation of automatically generated reviews that might be of low quality. Informed by this qualitative analysis, we identify criteria for rigorous evaluation of biomedical LLMs aligned with domain expert views.

Summarizing, Simplifying, and Synthesizing Medical Evidence Using GPT-3 (with Varying Success)

Large language models, particularly GPT-3, are able to produce high quality summaries of general domain news articles in few- and zero-shot settings. However, it is unclear if such models are similarly capable in more specialized, high-stakes domains such as biomedicine. In this paper, we enlist domain experts (individuals with medical training) to evaluate summaries of biomedical articles generated by GPT-3, given zero supervision. We consider both single- and multi-document settings. In the former, GPT-3 is tasked with generating regular and plain-language summaries of articles describing randomized controlled trials; in the latter, we assess the degree to which GPT-3 is able to \emph{synthesize} evidence reported across a collection of articles. We design an annotation scheme for evaluating model outputs, with an emphasis on assessing the factual accuracy of generated summaries. We find that while GPT-3 is able to summarize and simplify single biomedical articles faithfully, it struggles to provide accurate aggregations of findings over multiple documents. We release all data and annotations used in this work.

Do Multi-Document Summarization Models Synthesize?

Multi-document summarization entails producing concise synopses of collections of inputs. For some applications, the synopsis should accurately \emph{synthesize} inputs with respect to a key property or aspect. For example, a synopsis of film reviews all written about a particular movie should reflect the average critic consensus. As a more consequential example, consider narrative summaries that accompany biomedical \emph{systematic reviews} of clinical trial results. These narratives should fairly summarize the potentially conflicting results from individual trials. In this paper we ask: To what extent do modern multi-document summarization models implicitly perform this type of synthesis? To assess this we perform a suite of experiments that probe the degree to which conditional generation models trained for summarization using standard methods yield outputs that appropriately synthesize inputs. We find that existing models do partially perform synthesis, but do so imperfectly. In particular, they are over-sensitive to changes in input ordering and under-sensitive to changes in input compositions (e.g., the ratio of positive to negative movie reviews). We propose a simple, general method for improving model synthesis capabilities by generating an explicitly diverse set of candidate outputs, and then selecting from these the string best aligned with the expected aggregate measure for the inputs, or \emph{abstaining} when the model produces no good candidate. This approach improves model synthesis performance. We hope highlighting the need for synthesis (in some summarization settings), motivates further research into multi-document summarization methods and learning objectives that explicitly account for the need to synthesize.

What Would it Take to get Biomedical QA Systems into Practice?

Medical question answering (QA) systems have the potential to answer clinicians uncertainties about treatment and diagnosis on demand, informed by the latest evidence. However, despite the significant progress in general QA made by the NLP community, medical QA systems are still not widely used in clinical environments. One likely reason for this is that clinicians may not readily trust QA system outputs, in part because transparency, trustworthiness, and provenance have not been key considerations in the design of such models. In this paper we discuss a set of criteria that, if met, we argue would likely increase the utility of biomedical QA systems, which may in turn lead to adoption of such systems in practice. We assess existing models, tasks, and datasets with respect to these criteria, highlighting shortcomings of previously proposed approaches and pointing toward what might be more usable QA systems.

Paragraph-level Simplification of Medical Texts

We consider the problem of learning to simplify medical texts. This is important because most reliable, up-to-date information in biomedicine is dense with jargon and thus practically inaccessible to the lay audience. Furthermore, manual simplification does not scale to the rapidly growing body of biomedical literature, motivating the need for automated approaches. Unfortunately, there are no large-scale resources available for this task. In this work we introduce a new corpus of parallel texts in English comprising technical and lay summaries of all published evidence pertaining to different clinical topics. We then propose a new metric based on likelihood scores from a masked language model pretrained on scientific texts. We show that this automated measure better differentiates between technical and lay summaries than existing heuristics. We introduce and evaluate baseline encoder-decoder Transformer models for simplification and propose a novel augmentation to these in which we explicitly penalize the decoder for producing "jargon" terms; we find that this yields improvements over baselines in terms of readability.

Understanding Clinical Trial Reports: Extracting Medical Entities and Their Relations

The best evidence concerning comparative treatment effectiveness comes from clinical trials, the results of which are reported in unstructured articles. Medical experts must manually extract information from articles to inform decision-making, which is time-consuming and expensive. Here we consider the end-to-end task of both (a) extracting treatments and outcomes from full-text articles describing clinical trials (entity identification) and, (b) inferring the reported results for the former with respect to the latter (relation extraction). We introduce new data for this task, and evaluate models that have recently achieved state-of-the-art results on similar tasks in Natural Language Processing. We then propose a new method motivated by how trial results are typically presented that outperforms these purely data-driven baselines. Finally, we run a fielded evaluation of the model with a non-profit seeking to identify existing drugs that might be re-purposed for cancer, showing the potential utility of end-to-end evidence extraction systems.

Generating (Factual?) Narrative Summaries of RCTs: Experiments with Neural Multi-Document Summarization

We consider the problem of automatically generating a narrative biomedical evidence summary from multiple trial reports. We evaluate modern neural models for abstractive summarization of relevant article abstracts from systematic reviews previously conducted by members of the Cochrane collaboration, using the authors conclusions section of the review abstract as our target. We enlist medical professionals to evaluate generated summaries, and we find that modern summarization systems yield consistently fluent and relevant synopses, but that they are not always factual. We propose new approaches that capitalize on domain-specific models to inform summarization, e.g., by explicitly demarcating snippets of inputs that convey key findings, and emphasizing the reports of large and high-quality trials. We find that these strategies modestly improve the factual accuracy of generated summaries. Finally, we propose a new method for automatically evaluating the factuality of generated narrative evidence syntheses using models that infer the directionality of reported findings.

Trialstreamer: Mapping and Browsing Medical Evidence in Real-Time

We introduce Trialstreamer, a living database of clinical trial reports. Here we mainly describe the evidence extraction component; this extracts from biomedical abstracts key pieces of information that clinicians need when appraising the literature, and also the relations between these. Specifically, the system extracts descriptions of trial participants, the treatments compared in each arm (the interventions), and which outcomes were measured. The system then attempts to infer which interventions were reported to work best by determining their relationship with identified trial outcome measures. In addition to summarizing individual trials, these extracted data elements allow automatic synthesis of results across many trials on the same topic. We apply the system at scale to all reports of randomized controlled trials indexed in MEDLINE, powering the automatic generation of evidence maps, which provide a global view of the efficacy of different interventions combining data from all relevant clinical trials on a topic. We make all code and models freely available alongside a demonstration of the web interface.

Evidence Inference 2.0: More Data, Better Models

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.