Post Syndicated from Abhishek Pan original https://aws.amazon.com/blogs/big-data/how-zs-built-a-clinical-knowledge-repository-for-semantic-search-using-amazon-opensearch-service-and-amazon-neptune/

In this blog post, we will highlight how ZS Associates used multiple AWS services to build a highly scalable, highly performant, clinical document search platform. This platform is an advanced information retrieval system engineered to assist healthcare professionals and researchers in navigating vast repositories of medical documents, medical literature, research articles, clinical guidelines, protocol documents, activity logs, and more. The goal of this search platform is to locate specific information efficiently and accurately to support clinical decision-making, research, and other healthcare-related activities by combining queries across all the different types of clinical documentation.

ZS is a management consulting and technology firm focused on transforming global healthcare. We use leading-edge analytics, data, and science to help clients make intelligent decisions. We serve clients in a wide range of industries, including pharmaceuticals, healthcare, technology, financial services, and consumer goods. We developed and host several applications for our customers on Amazon Web Services (AWS). ZS is also an AWS Advanced Consulting Partner as well as an Amazon Redshift Service Delivery Partner. As it relates to the use case in the post, ZS is a global leader in integrated evidence and strategy planning (IESP), a set of services that help pharmaceutical companies to deliver a complete and differentiated evidence package for new medicines.

ZS uses several AWS service offerings across the variety of their products, client solutions, and services. AWS services such as Amazon Neptune and Amazon OpenSearch Service form part of their data and analytics pipelines, and AWS Batch is used for long-running data and machine learning (ML) processing tasks.

Clinical data is highly connected in nature, so ZS used Neptune, a fully managed, high performance graph database service built for the cloud, as the database to capture the ontologies and taxonomies associated with the data that formed the supporting a knowledge graph. For our search requirements, We have used OpenSearch Service, an open source, distributed search and analytics suite.

About the clinical document search platform

Clinical documents comprise of a wide variety of digital records including:

• Study protocols
• Evidence gaps
• Clinical activities
• Publications

Within global biopharmaceutical companies, there are several key personas who are responsible to generate evidence for new medicines. This evidence supports decisions by payers, health technology assessments (HTAs), physicians, and patients when making treatment decisions. Evidence generation is rife with knowledge management challenges. Over the life of a pharmaceutical asset, hundreds of studies and analyses are completed, and it becomes challenging to maintain a good record of all the evidence to address incoming questions from external healthcare stakeholders such as payers, providers, physicians, and patients. Furthermore, almost none of the information associated with evidence generation activities (such as health economics and outcomes research (HEOR), real-world evidence (RWE), collaboration studies, and investigator sponsored research (ISR)) exists as structured data; instead, the richness of the evidence activities exists in protocol documents (study design) and study reports (outcomes). Therein lies the irony—teams who are in the business of knowledge generation struggle with knowledge management.

ZS unlocked new value from unstructured data for evidence generation leads by applying large language models (LLMs) and generative artificial intelligence (AI) to power advanced semantic search on evidence protocols. Now, evidence generation leads (medical affairs, HEOR, and RWE) can have a natural-language, conversational exchange and return a list of evidence activities with high relevance considering both structured data and the details of the studies from unstructured sources.

Overview of solution

The solution was designed in layers. The document processing layer supports document ingestion and orchestration. The semantic search platform (application) layer supports backend search and the user interface. Multiple different types of data sources, including media, documents, and external taxonomies, were identified as relevant for capture and processing within the semantic search platform.

Document processing solution framework layer

All components and sub-layers are orchestrated using Amazon Managed Workflows for Apache Airflow. The pipeline in Airflow is scaled automatically based on the workload using Batch. We can broadly divide layers here as shown in the following figure:

Data crawling:

In the data crawling layer, documents are retrieved from a specified source SharePoint location and deposited into a designated Amazon Simple Storage Service (Amazon S3) bucket. These documents could be in variety of formats, such as PDF, Microsoft Word, and Excel, and are processed using format-specific adapters.

Data ingestion:

• The data ingestion layer is the first step of the proposed framework. At this later, data from a variety of sources smoothly enters the system’s advanced processing setup. In the pipeline, the data ingestion process takes shape through a thoughtfully structured sequence of steps.
• These steps include creating a unique run ID each time a pipeline is run, managing natural language processing (NLP) model versions in the versioning table, identifying document formats, and ensuring the health of NLP model services with a service health check.
• The process then proceeds with the transfer of data from the input layer to the landing layer, creation of dynamic batches, and continuous tracking of document processing status throughout the run. In case of any issues, a failsafe mechanism halts the process, enabling a smooth transition to the NLP phase of the framework.

Database ingestion:

The reporting layer processes the JSON data from the feature extraction layer and converts it into CSV files. Each CSV file contains specific information extracted from dedicated sections of documents. Subsequently, the pipeline generates a triple file using the data from these CSV files, where each set of entities signifies relationships in a subject-predicate-object format. This triple file is intended for ingestion into Neptune and OpenSearch Service. In the full document embedding module, the document content is segmented into chunks, which are then transformed into embeddings using LLMs such as llama-2 and BGE. These embeddings, along with metadata such as the document ID and page number, are stored in OpenSearch Service. We use various chunking strategies to enhance text comprehension. Semantic chunking divides text into sentences, grouping them into sets, and merges similar ones based on embeddings.

Agentic chunking uses LLMs to determine context-driven chunk sizes, focusing on proposition-based division and simplifying complex sentences. Additionally, context and document aware chunking adapts chunking logic to the nature of the content for more effective processing.

NLP:

The NLP layer serves as a crucial component in extracting specific sections or entities from documents. The feature extraction stage proceeds with localization, where sections are identified within the document to narrow down the search space for further tasks like entity extraction. LLMs are used to summarize the text extracted from document sections, enhancing the efficiency of this process. Following localization, the feature extraction step involves extracting features from the identified sections using various procedures. These procedures, prioritized based on their relevance, use models like Llama-2-7b, mistral-7b, Flan-t5-xl, and Flan-T5-xxl to extract important features and entities from the document text.

The auto-mapping phase ensures consistency by mapping extracted features to standard terms present in the ontology. This is achieved through matching the embeddings of extracted features with those stored in the OpenSearch Service index. Finally, in the Document Layout Cohesion step, the output from the auto-mapping phase is adjusted to aggregate entities at the document level, providing a cohesive representation of the document’s content.

Semantic search platform application layer

This layer, shown in the following figure, uses Neptune as the graph database and OpenSearch Service as the vector engine.

Amazon OpenSearch Service:

OpenSearch Service served the dual purpose of facilitating full-text search and embedding-based semantic search. The OpenSearch Service vector engine capability helped to drive Retrieval-Augmented Generation (RAG) workflows using LLMs. This helped to provide a summarized output for search after the retrieval of a relevant document for the input query. The method used for indexing embeddings was FAISS.

OpenSearch Service domain details:

• Version of OpenSearch Service: 2.9
• Number of nodes: 1
• Instance type: r6g.2xlarge.search
• Volume size: Gp3: 500gb
• Number of Availability Zones: 1
• Dedicated master node: Enabled
• Number of Availability Zones: 3
• No of master Nodes: 3
• Instance type(Master Node) : r6g.large.search

To determine the nearest neighbor, we employ the Hierarchical Navigable Small World (HNSW) algorithm. We used the FAISS approximate k-NN library for indexing and searching and the Euclidean distance (L2 norm) for distance calculation between two vectors.

Amazon Neptune:

Neptune enables full-text search (FTS) through the integration with OpenSearch Service. A native streaming service for enabling FTS provided by AWS was established to replicate data from Neptune to OpenSearch Service. Based on the business use case for search, a graph model was defined. Considering the graph model, subject matter experts from the ZS domain team curated custom taxonomy capturing hierarchical flow of classes and sub-classes pertaining to clinical data. Open source taxonomies and ontologies were also identified, which would be part of the knowledge graph. Sections and entities were identified to be extracted from clinical documents. An unstructured document processing pipeline developed by ZS processed the documents in parallel and populated triples in RDF format from documents for Neptune ingestion.

The triples are created in such a way that semantically similar concepts are linked—hence creating a semantic layer for search. After the triples files are created, they’re stored in an S3 bucket. Using the Neptune Bulk Loader, we were able to load millions of triples to the graph.

Neptune ingests both structured and unstructured data, simplifying the process to retrieve content across different sources and formats. At this point, we were able to discover previously unknown relationships between the structured and unstructured data, which was then made available to the search platform. We used SPARQL query federation to return results from the enriched knowledge graph in the Neptune graph database and integrated with OpenSearch Service.

Neptune was able to automatically scale storage and compute resources to accommodate growing datasets and concurrent API calls. Presently, the application sustains approximately 3,000 daily active users. Concurrently, there is an observation of approximately 30–50 users initiating queries simultaneously within the application environment. The Neptune graph accommodates a substantial repository of approximately 4.87 million triples. The triples count is increasing because of our daily and weekly ingestion pipeline routines.

Neptune configuration:

• Instance Class: db.r5d.4xlarge
• Engine version: 1.2.0.1

LLMs:

Large language models (LLMs) like Llama-2, Mistral and Zephyr are used for extraction of sections and entities. Models like Flan-t5 were also used for extraction of other similar entities used in the procedures. These selected segments and entities are crucial for domain-specific searches and therefore receive higher priority in the learning-to-rank algorithm used for search.

Additionally, LLMs are used to generate a comprehensive summary of the top search results.

The LLMs are hosted on Amazon Elastic Kubernetes Service (Amazon EKS) with GPU-enabled node groups to ensure rapid inference processing. We’re using different models for different use cases. For example, to generate embeddings we deployed a BGE base model, while Mistral, Llama2, Zephyr, and others are used to extract specific medical entities, perform part extraction, and summarize search results. By using different LLMs for distinct tasks, we aim to enhance accuracy within narrow domains, thereby improving the overall relevance of the system.

Fine tuning :

Already fine-tuned models on pharma-specific documents were used. The models used were:

• PharMolix/BioMedGPT-LM-7B (finetuned LLAMA-2 on medical)
• emilyalsentzer/Bio_ClinicalBERT
• stanford-crfm/BioMedLM
• microsoft/biogpt

Re ranker, sorter, and filter stage:

Remove any stop words and special characters from the user input query to ensure a clean query. Upon pre-processing the query, create combinations of search terms by forming combinations of terms with varying n-grams. This step enriches the search scope and improves the chances of finding relevant results. For instance, if the input query is “machine learning algorithms,” generating n-grams could result in terms like “machine learning,” “learning algorithms,” and “machine learning algorithms”. Run the search terms simultaneously using the search API to access both Neptune graph and OpenSearch Service indexes. This hybrid approach broadens the search coverage, tapping into the strengths of both data sources. Specific weight is assigned to each result obtained from the data sources based on the domain’s specifications. This weight reflects the relevance and significance of the result within the context of the search query and the underlying domain. For example, a result from Neptune graph might be weighted higher if the query pertains to graph-related concepts, i.e. the search term is related directly to the subject or object of a triple, whereas a result from OpenSearch Service might be given more weightage if it aligns closely with text-based information. Documents that appear in both Neptune graph and OpenSearch Service receive the highest priority, because they likely offer comprehensive insights. Next in priority are documents exclusively sourced from the Neptune graph, followed by those solely from OpenSearch Service. This hierarchical arrangement ensures that the most relevant and comprehensive results are presented first. After factoring in these considerations, a final score is calculated for each result. Sorting the results based on their final scores ensures that the most relevant information is presented in the top n results.

Final UI

An evidence catalogue is aggregated from disparate systems. It provides a comprehensive repository of completed, ongoing and planned evidence generation activities. As evidence leads make forward-looking plans, the existing internal base of evidence is made readily available to inform decision-making.

The following video is a demonstration of an evidence catalog:

Customer impact

When completed, the solution provided the following customer benefits:

• The search on multiple data source (structured and unstructured documents) enables visibility of complex hidden relationships and insights.
• Clinical documents often contain a mix of structured and unstructured data. Neptune can store structured information in a graph format, while the vector database can handle unstructured data using embeddings. This integration provides a comprehensive approach to querying and analyzing diverse clinical information.
• By building a knowledge graph using Neptune, you can enrich the clinical data with additional contextual information. This can include relationships between diseases, treatments, medications, and patient records, providing a more holistic view of healthcare data.
• The search application helped in staying informed about the latest research, clinical developments, and competitive landscape.
• This has enabled customers to make timely decisions, identify market trends, and help positioning of products based on a comprehensive understanding of the industry.
• The application helped in monitoring adverse events, tracking safety signals, and ensuring that drug-related information is easily accessible and understandable, thereby supporting pharmacovigilance efforts.
• The search application is currently running in production with 3000 active users.

Customer success criteria

The following success criteria were use to evaluate the solution:

• Quick, high accuracy search results: The top three search results were 99% accurate with an overall latency of less than 3 seconds for users.
• Identified, extracted portions of the protocol: The sections identified has a precision of 0.98 and recall of 0.87.
• Accurate and relevant search results based on simple human language that answer the user’s question.
• Clear UI and transparency on which portions of the aligned documents (protocol, clinical study reports, and publications) matched the text extraction.
• Knowing what evidence is completed or in-process reduces redundancy in newly proposed evidence activities.

Challenges faced and learnings

We faced two main challenges in developing and deploying this solution.

Large data volume

The unstructured documents were required to be embedded completely and OpenSearch Service helped us achieve this with the right configuration. This involved deploying OpenSearch Service with master nodes and allocating sufficient storage capacity for embedding and storing unstructured document embeddings entirely. We stored up to 100 GB of embeddings in OpenSearch Service.

Inference time reduction

In the search application, it was vital that the search results were retrieved with lowest possible latency. With the hybrid graph and embedding search, this was challenging.

We addressed high latency issues by using an interconnected framework of graphs and embeddings. Each search method complemented the other, leading to optimal results. Our streamlined search approach ensures efficient queries of both the graph and the embeddings, eliminating any inefficiencies. The graph model was designed to minimize the number of hops required to navigate from one entity to another, and we improved its performance by avoiding the storage of bulky metadata. Any metadata too large for the graph was stored in OpenSearch, which served as our metadata store for graph and vector store for embeddings. Embeddings were generated using context-aware chunking of content to reduce the total embedding count and retrieval time, resulting in efficient querying with minimal inference time.

The Horizontal Pod Autoscaler (HPA) provided by Amazon EKS, intelligently adjusts pod resources based on user-demand or query loads, optimizing resource utilization and maintaining application performance during peak usage periods.

Conclusion

In this post, we described how to build an advanced information retrieval system designed to assist healthcare professionals and researchers in navigating through a diverse range of medical documents, including study protocols, evidence gaps, clinical activities, and publications. By using Amazon OpenSearch Service as a distributed search and vector database and Amazon Neptune as a knowledge graph, ZS was able to remove the undifferentiated heavy lifting associated with building and maintaining such a complex platform.

If you’re facing similar challenges in managing and searching through vast repositories of medical data, consider exploring the powerful capabilities of OpenSearch Service and Neptune. These services can help you unlock new insights and enhance your organization’s knowledge management capabilities.

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About the authors

Abhishek Pan is a Sr. Specialist SA-Data working with AWS India Public sector customers. He engages with customers to define data-driven strategy, provide deep dive sessions on analytics use cases, and design scalable and performant analytical applications. He has 12 years of experience and is passionate about databases, analytics, and AI/ML. He is an avid traveler and tries to capture the world through his lens.

Gourang Harhare is a Senior Solutions Architect at AWS based in Pune, India. With a robust background in large-scale design and implementation of enterprise systems, application modernization, and cloud native architectures, he specializes in AI/ML, serverless, and container technologies. He enjoys solving complex problems and helping customer be successful on AWS. In his free time, he likes to play table tennis, enjoy trekking, or read books

Kevin Phillips is a Neptune Specialist Solutions Architect working in the UK. He has 20 years of development and solutions architectural experience, which he uses to help support and guide customers. He has been enthusiastic about evangelizing graph databases since joining the Amazon Neptune team, and is happy to talk graph with anyone who will listen.

Sandeep Varma is a principal in ZS’s Pune, India, office with over 25 years of technology consulting experience, which includes architecting and delivering innovative solutions for complex business problems leveraging AI and technology. Sandeep has been critical in driving various large-scale programs at ZS Associates. He was the founding member the Big Data Analytics Centre of Excellence in ZS and currently leads the Enterprise Service Center of Excellence. Sandeep is a thought leader and has served as chief architect of multiple large-scale enterprise big data platforms. He specializes in rapidly building high-performance teams focused on cutting-edge technologies and high-quality delivery.

Alex Turok has over 16 years of consulting experience focused on global and US biopharmaceutical companies. Alex’s expertise is in solving ambiguous, unstructured problems for commercial and medical leadership. For his clients, he seeks to drive lasting organizational change by defining the problem, identifying the strategic options, informing a decision, and outlining the transformation journey. He has worked extensively in portfolio and brand strategy, pipeline and launch strategy, integrated evidence strategy and planning, organizational design, and customer capabilities. Since joining ZS, Alex has worked across marketing, sales, medical, access, and patient services and has touched over twenty therapeutic categories, with depth in oncology, hematology, immunology and specialty therapeutics.