Toward a Reference Architecture for Intelligent Systems in Clinical Care

A Software Architecture for Precision Medicine

Intelligent systems in clinical care leverage the latest innovations in machine learning, real-time data stream mining, visual analytics, natural language processing, ontologies, production rule systems, and cloud computing to provide clinicians with the best knowledge and information at the point of care for effective clinical decision making. In this post, I propose a unified open reference architecture that combines all these technologies into a hybrid cognitive system for clinical decision support. Indeed, truly intelligent systems are capable of reasoning. The goal is not to replace clinicians, but instead to provide them with cognitive support during clinical decision making. Furthermore, Intelligent Personal Assistants (IPAs) such as Apple's Siri, Google's Google Now, and Microsoft's Cortana have raised our expectations on how intelligent systems interact with users through voice and natural language.

In the strict sense of the term, a reference architecture should be abstracted away from concrete technology implementation. However in order to enable a better understanding of the proposed approach, I take liberty in explaining how available open source software can be used to realize the intent of the architecture. There is an urgent need for an open and interoperable architecture which can be deployed across devices and platforms. Unfortunately, this is not the case today with solutions like Apple's HealthKit and ResearchKit.

The specific open source software mentioned in this post can be substituted with other tools which provide similar capabilities. The following diagram is a depiction of the architecture (click to enlarge).

 

Clinical Data Sources

Clinical data sources are represented on the left of the architecture diagram. Examples include electronic medical record systems (EMR) commonly used in routine clinical care, clinical genome databases, genome variant knowledge bases, medical imaging databases, data from medical devices and wearable sensors, and unstructured data sources such as biomedical literature databases. The approach implements the Lambda Architecture enabling both batch and real-time data stream processing and mining.

Predictive Modeling, Real-Time Data Stream Mining, and Big Data Genomics

The back-end provides various tools and frameworks for advanced analytics and decision management. The analytics workbench includes tools for creating predictive models and data streaming mining. The decision management workbench includes a production rule system (providing seamless integration with clinical events and processes) and an ontology editor.

The incoming clinical data likely meet the Big Data criteria of volume, velocity, and variety (this is particularly true for physiological time series from wearable sensors). Therefore, specialized frameworks for large scale cluster computing like Apache Spark are used to analyze and process the data. Statistical computing and Machine Learning tools like R are used here as well. The goal is knowledge and patterns discovery using Machine Learning model builders like Decision Trees, k-Means Clustering, Logistic Regression, Support Vector Machines (SVMs), Bayesian Networks, Neural Networks, and the more recent Deep Learning techniques. The latter hold great promise in applications such as Natural Language Processing (NLP), medical image analysis, and speech recognition.

These Machine Learning algorithms can support diagnosis, prognosis, simulation, anomaly detection, care alerting, and care planning. For example, anomaly detection can be performed at scale using the k-means clustering machine learning algorithm in Apache Spark. In addition, Apache Spark allows the implementation of the Lambda Architecture and can also be used for genome Big Data analysis at scale.

In another post titled How Good is Your Crystal Ball?: Utility, Methodology, and Validity of Clinical Prediction Models, I discuss quantitative measures of performance for clinical prediction models.

Visual Analytics

Visual Analytics tools like D3.js, rCharts, ploty, googleVis, ggplot2, and ggvis can help obtain deep insight for effective understanding, reasoning, and decision making through the visual exploration of massive, complex, and often ambiguous data. Of particular interest is Visual Analytics of real-time data streams like physiological time series. As a multidisciplinary field, Visual Analytics combines several disciplines such as human perception and cognition, interactive graphic design, statistical computing, data mining, spatio-temporal data analysis, and even Art. For example, similar to Minard's map of the Russian Campaign of 1812-1813 (see graphic below), Visual Analytics can help in comparing different interventions and care pathways and their respective clinical outcomes over a certain period of time by displaying causes, variables, comparisons, and explanations.

Production Rule System, Ontology Reasoning, and NLP

The architecture also includes a production rule engine and an ontology editor (Drools and Protégé respectively). This is done in order to leverage existing clinical domain knowledge available from clinical practice guidelines (CPGs) and biomedical ontologies like SNOMED CT.  This approach complements machine learning algorithms' probabilistic approach to clinical decision making under uncertainty. The production rule system can translate CPGs into executable rules which are fully integrated with clinical processes (workflows) and events. The ontologies can provide automated reasoning capabilities for decision support.

NLP includes capabilities such as:

• Text classification, text clustering, document and passage retrieval, text summarization, and more advanced clinical question answering (CQA) capabilities which can be useful for satisfying clinicians' information needs at the point of care; and
• Named entity recognition (NER) for extracting concepts from clinical notes.

The data tier supports the efficient storage of large amounts of time series data and is implemented with tools like Cassandra and HBase. The system can run in the cloud, for example using the Amazon Elastic Compute Cloud (EC2). For real-time processing of distributed data streams, cloud-based solutions like Amazon Kinesis and Lambda can be used.

 

Clinical Decision Services

The clinical decision services provide intelligence at the point of care typically using deployed predictive models, clinical rules, text mining outputs, and ontology reasoners. For example, Machine Learning algorithms can be exported in predictive markup language (PMML) format for run-time scoring based on the clinical data of individual patients, enabling what is referred to as Personalized Medicine. Clinical decision services include:

• Diagnosis and prognosis
• Simulation
• Anomaly detection 
• Data visualization
• Information retrieval (e.g., clinical question answering)
• Alerts and reminders
• Support for care planning processes.

The clinical decision services can be deployed in the cloud as well. Other clinical systems can consume these services through a SOAP or REST-based web service interface (using the HL7 vMR and DSS specifications for interoperability) and single sign-on (SSO) standards like SAML2 and OpenID Connect.

Intelligent Personal Assistants (IPAs)

Clinical decision services can also be delivered to patients and clinicians through IPAs. IPAs can accept inputs in the form of voice, images, and user's context and respond in natural language. IPAs are also expanding to wearable technologies such as smart watches and glasses. The precision of speech recognition, natural language processing, and computer vision is improving rapidly with the adoption of Deep Learning techniques and tools. Accelerated hardware technologies like GPUs and FPGAs are improving the performance and reducing the cost of deploying these systems at scale.

Hexagonal, Reactive, and Secure Architecture

Intelligent Health IT systems are not just capable of discovering knowledge and patterns in data. They are also scalable, resilient, responsive, and secure. To achieve these objectives, several architectural patterns have emerged during the last few years:

• Domain Driven Design (DDD) puts the emphasis on the core domain and domain logic and recommends a layered architecture (typically user interface, application, domain, and infrastructure) with each layer having well defined responsibilities and interfaces for interacting with other layers. Models exist within "bounded contexts". These "bounded contexts" communicate with each other typically through messaging and web services using HL7 standards for interoperability.


• The Hexagonal Architecture defines "ports and adapters" as a way to design, develop, and test an application in a way that is independent of the various clients, devices, transport protocols (HTTP, REST, SOAP, MQTT, etc.), and even databases that could be used to consume its services in the future. This is particularly important in the era of the Internet of Things in healthcare.


• Microservices consist in decomposing large monolithic applications into smaller services following good old principles of service-oriented design and single responsibility to achieve modularity, maintainability, scalability, and ease of deployment (for example, using Docker).


• CQRS/ES: Command Query Responsibility Segregation (CQRS) and Event Sourcing (ES) are two architectural patterns which consist in the use of event-driven messaging and an Event Store for separating commands (write-side) from queries (read-side) relying on the principle of Eventual Consistency. CQRS/ES can be implemented in combination with microservices to deliver new capabilities such as temporal queries, behavioral analysis, complex audit logs, and real-time notifications and alerts.


• Functional Programming: Functional Programming languages like Scala have several benefits that are particularly important for applying Machine Learning algorithms on large data sets. Like functions in mathematics, functions in Scala have no side effects. This provides referential transparency. Machine Learning algorithms are in fact based on Linear Algebra and Calculus. Scala supports high-order functions as well. Variables are immutable witch greatly simplifies concurrency. For all those reasons, Machine Learning libraries like Apache Mahout have embraced Scala, moving away from the Java MapReduce paradigm.


• Reactive Architecture: The Reactive Manifesto makes the case for a new breed of applications called "Reactive Applications". According to the manifesto, the Reactive Application architecture allows developers to build "systems that are event-driven, scalable, resilient, and responsive."  Leading frameworks that support Reactive Programming include Akka and RxJava. The latter is a library for composing asynchronous and event-based programs using observable sequences. RxJava is a Java port (with a Scala adaptor) of the original Rx (Reactive Extensions) for .NET created by Erik Meijer.
  
  Based on the Actor Model and built in Scala, Akka is a framework for building highly concurrent, asynchronous, distributed, and fault tolerant event-driven applications on the JVM. Akka offers location transparency, fault tolerance, asynchronous message passing, and a non-deterministic share-nothing architecture. Akka Cluster provides a fault-tolerant decentralized peer-to-peer based cluster membership service with no single point of failure or single point of bottleneck.
  
  Also built with Scala, Apache Kafka is a scalable message broker which provides high-throughput, fault-tolerance, built-in partitioning, and replication  for processing real-time data streams. In the reference architecture, the ingestion layer is implemented with Akka and Apache Kafka.

• Web Application Security: special attention is given to security across all layers, notably the proper implementation of authentication, authorization, encryption, and audit logging. The implementation of security is also driven by deep knowledge of application security patterns, threat modeling, and enforcing security best practices (e.g., OWASP Top Ten and CWE/SANS Top 25 Most Dangerous Software Errors) as part of the continuous delivery process.

An Interface that Works across Devices and Platforms

The front-end uses a Mobile First approach and a Single Page Application (SPA) architecture with Javascript-based frameworks like AngularJS to create very responsive user experiences. It also allows us to bring the following software engineering best practices to the front-end:

• Dependency Injection
• Test-Driven Development (Jasmine, Karma, PhantomJS)
• Package Management (Bower or npm)
• Build system and Continuous Integration (Grunt or Gulp.js)
• Static Code Analysis (JSLint and JSHint), and 
• End-to-End Testing (Protractor). 

For mobile devices, Apache Cordova can be used to access native functions when desired. The main goal is to provide a user interface that works across devices and platforms such as iOS, Android, and Windows Phone.

Interoperability

Interoperability will always be a key requirement in clinical systems. Interoperability is needed between all players in the healthcare ecosystem including providers, payers, labs, knowledge artifact developers, quality measure developers, and public health agencies like the CDC. These standards exist today and are implementation-ready. However, only health IT buyers have the leverage to demand interoperability from their vendors.

Standards related to clinical decision support (CDS) include:

• The HL7 Fast Healthcare Interoperability Resources (FHIR)
• The HL7 virtual Medical Record (vMR)
• The HL7 Decision Support Services (DSS) specification
• The HL7 CDS Knowledge Artifact specification
• The DMG Predictive Model Markup Language (PMML) specification.

Overcoming Barriers to Adoption

In a previous post, I discussed a practical approach to addressing challenges to the adoption of clinical decision support (CDS) systems.

Natural Language Processing (NLP) for Clinical Decision Support: A Practical Approach

A significant portion of the electronic documentation of clinical care is captured in the form of unstructured narrative text like psychotherapy and progress notes. Despite the big push to adopt structured data entry (as required by the Meaningful Use incentive program for example), many clinicians still like to document care using free narrative text. The advantage of using narrative text as opposed to coded entries is that narrative text can tell the story of the patient and the care provided particularly in complex cases. My opinion is that free narrative text should be used to complement coded entries when necessary to capture relevant information.

Furthermore, medical knowledge is expanding very rapidly. For example, PubMed has more than 24 millions citations for biomedical literature from MEDLINE, life science journals, and online books. It is impossible for the human brain to keep up with that amount of knowledge. These unstructured sources of knowledge contain the scientific evidence that is required for effective clinical decision making in what is referred to as Evidence-Based Medicine (EBM).

In this blog, I discuss two practical applications of Natural Language Processing (NLP). The first is the use of NLP tools and techniques to automatically extract clinical concepts and other insight from clinical notes for the purpose of providing treatment recommendations in Clinical Decision Support (CDS) systems. The second is the use of text analytics techniques like clustering and summarization for Clinical Question Answering (CQA).

The emphasis of this post is on a practical approach using freely available and mature open source tools as opposed to an academic or theoretical approach. For a theoretical treatment of the subject, please refer to the book Speech and Language Processing by Daniel Jurafsky and James Martin.

Clinical NLP with Apache cTAKES

Based on the Apache Unstructured Information Management Architecture (UIMA) framework and the Apache OpenNLP natural language processing toolkit, Apache cTAKES provides a modular architecture utilizing both rule-based and machine learning techniques for information extraction from clinical notes. cTAKES can extract named entities (clinical concepts) from clinical notes in plain text or HL7 CDA format and map these entities to various dictionaries including the following Unified Medical Language System (UMLS) semantic types: diseases/disorders, signs/symptoms, anatomical sites, procedures, and medications.

cTAKES includes the following key components which can be assembled to create processing pipelines:

• Sentence boundary detector based on the OpenNLP Maximum Entropy (ME) sentence detector.
• Tokenizor
• Normalizer using the National Library of Medicine's Lexical Variant Generation (LVG) tool
• Part-of-speech (POS) tagger
• Shallow parser
• Named Entity Recognition (NER) annotator using dictionary look-up to UMLS concepts and semantic types. The Drug NER can extract drug entities and their attributes such as dosage, strength, route, etc.
• Assertion module which determines the subject of the statement (e.g., is the subject of the statement the patient or a parent of the patient) and whether a named entity or event is negated (e.g., does the presence of the word "depression" in the text implies that the patient has depression).

Apache cTAKES 3.2 has added YTEX, a set of extensions developed at Yale University which provide integration with MetaMap, semantic similarity, export to Machine Learning packages like Weka and R, and feature engineering.

The following diagram from the Apache cTAKES Wiki provides an overview of these components and their dependencies (click to enlarge):

Source: Apache cTAKES wiki

Massively Parallel Clinical Text Analytics in the Cloud with GATECloud

The General Architecture for Text Engineering (GATE) is a mature, comprehensive, and open source text analytics platform. GATE is a family of tools which includes:

• GATE Developer: an integrated development environment (IDE) for language processing components with a comprehensive set of available plugins called CREOLE (Collection of REusable Objects for Language Engineering). 
• GATE Embedded: an object library for embedding services developed with GATE Developer into third-party applications.
• GATE Teamware: a collaborative semantic annotation environment based on a workflow engine for creating manually annotated corpora for applying machine learning algorithms. 
• GATE Mímir: the "Multi-paradigm Information Management Index and Repository" which supports a multi-paradigm approach to index and search over text, ontologies, and semantic metadata.
• GATE Cloud: a massively parallel clinical text analytics platform (Platform as a Service or PaaS) built on the Amazon AWS Cloud.

What makes GATE particularly attractive is the recent addition of GATECloud.net PaaS which can boost the productivity of people involved in large scale text analytics tasks.

 

Clustering, Classification, Text Summarization, and Clinical Question Answering (CQA)

 

An unsupervised machine learning approach called Clustering can be used to classify large volumes of medical literature into groups (clusters) based on some similarity measure (such as the Euclidean distance). Clustering can be applied at the document, search result, and word/topic levels. Carrot2 and Apache Mahout are open source projects that provide several methods for document clustering. For example, the Latent Dirichlet Allocation learning algorithm in Apache Mahout automatically clusters words into topics and documents into mixtures of topics. Other clustering algorithms in Apache Mahout include: Canopy, Mean-Shift, Spectral, K-Means and Fuzzy K-Means. Apache Mahout is part of the Hadoop ecosystem and can therefore scale to very large volumes of unstructured text.

Document classification essentially consists in assigning predefined set of labels to documents. This can be achieved through supervised machine learning algorithms. Apache Mahout implements the Naive Bayes classifier.

Text summarization techniques can be used to present succinct and clinically relevant evidence to clinicians at the point of care. MEAD (http://www.summarization.com/mead/) is an open source project that implements multiple summarization algorithms. In the biomedical domain, SemRep is a program that extracts semantic predications (subject-relation-object triples) from biomedical free text. Subject and object arguments of each predication are concepts from the UMLS Metathesaurus and the relation is from the UMLS Semantic Network (e.g., TREATS, Co-OCCURS_WITH). The SemRep summarization provides a short summary of these concepts and their semantic relations.

AskHermes (Help clinicians to Extract and aRrticulate Multimedia information for answering clinical quEstionS) is a project that attempts to implement these techniques in the clinical domain. It allows clinicians to enter questions in natural language and uses the following unstructured information sources: MEDLINE abstracts, PubMed Central full-text articles, eMedicine documents, clinical guidelines, and Wikipedia articles.

The processing pipeline in AskHermes includes the following: Question Analysis, Related Questions Extraction, Information Retrieval, Summarization and Answer Presentation. AskHermes performs question classification using MMTx (MetaMap Technology Transfer) to map keywords to UMLS concepts and semantic types. Classification is achieved through supervised machine learning algorithms such as Support Vector Machine (SVM) and conditional random fields (CFRs). Summarization and answer presentation are based on clustering techniques. AskHermes is powered by open source components including: JBoss Seam, Weka, Mallet , Carrot2 , Lucene/Solr, and WordNet (a lexical database for the English language).

Enabling Scalable Realtime Healthcare Analytics with Apache Spark

Modern and massively parallel computing platforms can process humongous amounts of data in real time to obtain actionable insights for effective clinical decision making. In this blog, I discuss an emerging Big Data platform called Apache Spark and its application to remote real-time healthcare monitoring using data from medical devices and wearable sensors. The goal is to provide effective remote care for an increasingly aging population as well as public health surveillance.

The Apache Spark Framework

Apache Spark has emerged during the last couple of years as an innovative platform for Big Data and in-memory cluster computing capable of running programs up to 100x faster than traditional Hadoop MapReduce. Apache Spark is written in Scala, a functional programming language (see my previous post titled Navigating in Scala land). Spark also offers a Java and a Python APIs. The Scala API allows developers to interact with Spark by using very concise and expressive Scala code.

The Spark stack also includes the following integrated tools:

• Spark SQL which allows relational queries expressed in SQL, HiveQL, or Scala to be executed using Spark through a data abstraction called SchemaRDD. Supported data sources include Parquet files (a columnar storage format for Hadoop), JSON datasets, or data stored in Apache Hive.


• Spark Streaming which enables fault-tolerant stream processing of live data streams. Data can be ingested from many sources like Kafka, Flume, Twitter, ZeroMQ or plain old TCP sockets. The ingested data can be directly processed with Spark built-in Machine Learning algorithms.


• MLlib (Machine Learning Library) provides a library of practical Machine Learning algorithms including support vector machines (SVM), logistic regression, decision trees, naive Bayes, and k-means clustering.


• GraphX which provides graph-parallel computation for graph-analytics application like social networks.

Apache Spark can also play nicely with other frameworks within the Hadoop ecosystem. For example, it can run standalone or on a Hadoop 2's YARN cluster manager, on Amazon EC2 or a Mesos cluster manager. Spark can also read data from HFDS, HBase, Cassandra or any other Hadoop data source. Other noteworthy integrations include:

• SparkR, an R package allowing the use of Spark from R, a very popular open source software environment for statistical computing with more that 5800 packages including Machine Learning packages; and


• H2O-Sparkling which provides an integration with the H2O platform through in-memory sharing with Tachyon, a memory-centric distributed file system for data sharing across cluster frameworks. This allows Spark applications to leverage advanced distributed Machine Learning algorithms supported by the H2O platform like emerging Deep Learning algorithms.

 

Wearable Sensors for Remote Healthcare Monitoring 

Three factors are contributing to the availability of massive amounts of clinical data: the rising adoption of EHRs by providers thanks in part to the Meaningful Use incentive program; the increasing use of medical devices including wearable sensors used by patients outside of healthcare facilities; and medical knowledge (for example in the form of medical research literature).

One promising area in Healthcare Informatics where Big Data architectures like the one provided by Apache Spark can make a difference is in applications using data from wearable health monitoring sensors for anomaly detection, care alerting, diagnosis, care planning, and prediction. For example, anomaly detection can be performed at scale using the k-means clustering machine learning algorithm in Spark.

These sensors and devices are part of a larger trend called the "Internet of Things". They enable new capabilities such as remote health monitoring for personalized medicine and chronic care management for an increasingly aging population as well as public health surveillance for outbreaks and epidemics.

Wearable sensors can collect vital signs data like weight, temperature, blood pressure (BP), heart rate (HR), blood glucose (BG), respiratory rate (RR), electrocardiogram (ECG), oxygen saturation (SpO2), and Photoplethysmography (PPG). Spark Streaming can be used to perform real-time stream processing on sensors data and the data can be processed and analyzed using the Machine Learning algorithms available in MLlib and the other integrated frameworks like R and H2O. What makes Spark particularly suitable for this type of applications is that sensor data meet the Big Data criteria of volume, velocity, and variety.

Researchers predict that internet use on mobile phones will increase 20-fold in Africa in the next five years. The number of mobile subscriptions in sub-Saharan Africa is expected to reach 635 millions by the end of this year. This unprecedented level of connectivity (fueled in part by the historical lack of land line infrastructure) provides opportunities for effective public health surveillance and disease management in the developing world.

Apache Spark is the type of open source computing infrastructure that is needed for distributed, scalable, and real-time healthcare analytics for reducing healthcare costs and improving outcomes.

How I Make Technology Decisions

The open source community has responded to the increasing complexity of software systems by creating many frameworks which are supposed to facilitate the work of developing software. Software developers spend a considerable amount of time researching, learning, and integrating these frameworks to build new software products. Selecting the wrong technology can cost an organization millions of dollars. In this post, I describe my approach to selecting these frameworks. I also discuss the frameworks that have made it to my software development toolbox.

Understanding the Business

The first step is to build a strong understanding of the following:

• The business goals and challenges of the organization. For example, the healthcare industry is currently shifting to a value-based payment model in an increasingly tightening regulatory environment. Healthcare organizations are looking for a computing infrastructure that support new demands such as the Accountable Care Organization (ACO) model, patient-centered outcomes, patient engagement, care coordination, quality measures, bundled payments, and Patient-Centered Medical Homes (PCMH).


• The intended buyers and users of the system and their concerns. For example, what are their pain points? which devices are they using? and what are their security and privacy concerns?


• The standards and regulations of the industry.


• The competitive landscape in the industry. To build a system that is relevant, it is important to have some ideas about the following: what is the competition? what are the current capabilities of their systems? what is on their road map? and what are customers saying about their products. This knowledge can help shape a Blue Ocean Strategy.


• Emerging trends in technologies.

This type of knowledge comes with industry experience and a habit of continuously paying attention to these issues. For example, on a daily basis, I read industry news as well as scientific and technical publications. As a member of the American Medical Informatics Association (AMIA), I receive the latest issue of the Journal of the American Medical Informatics Association (JAMIA) which allows me to access cutting-edge research in medical informatics. I speak at industry conferences when possible and this allows me not only to hone my presentation skills, but also attend all sessions for free or at a discounted price. For the latest in software development, I turn to publications like InfoQ, DZone, and TechCrunch.

To better understand the users and their needs and concerns, I perform early usability testing (using sketches, wireframes, or mockups) to test design ideas and obtain feedback before actual development starts. For generating innovative design ideas, I recommend the following book: Universal Methods of Design: 100 Ways to Research Complex Problems, Develop Innovative Ideas, and Design Effective Solutions by Bruce Hanington and Bella Martin.

 

Architecting the Solution

Armed with a solid understanding of the business and technological landscape as well as the domain, I can start creating a solution architecture. Software development projects can be chaotic. Based on my experience working on many software development projects across industries, I found that Domain Driven Design (DDD) can help foster a disciplined approach to software development. For more on my experience with DDD, see my previous post entitled How Not to Build A Big Ball of Mud, Part 2.

Frameworks evolve over time. So, I make sure that the architecture is framework-agnostic and focused on supporting the domain. This allows me to retrofit the system in the future with new frameworks as they emerge.

 

Due Diligence

Software development is a rapidly evolving field. I keep my eyes on the radar and try not to drink the vendors Kool-Aid. For example, not all vendors have a good track record in supporting standards, interoperability, and cross-platform solutions.

The ThoughtWorks Technology Radar is an excellent source of information and analysis on emerging trends in software. Its contributors include software thought leaders like Martin Fowler and Rebecca Parson. I also look at surveys of the developers community to determine the popularity, community size, and usage statistics of competing frameworks and tools. Sites like InfoQ often conduct these types of surveys like the recent InfoQ survey on Top JavaScript MVC Frameworks. I also like Matt Raible's Comparing JVM Web Frameworks.

I value the opinion of recognized experts in the field of interest. I read their books, blogs, and watch their presentations. Before formulating my own position, I make sure that I read expert opinions on opposing sides of the argument. For example, in deciding on a pure Java EE vs. Spring Framework approach, I read arguments by experts on both sides (experts like Arun Gupta, Java EE Evangelist at Oracle and Adrian Colyer, CTO at SpringSource).

Finally, consider a peer review of the architecture using a methodology like the Architecture Tradeoff Analysis Method (ATAM). Simply going through the exercise of explaining the architecture to stakeholders and receiving feedback can significantly help in improving it.

Rapid Prototyping 

 

It's generally a good idea to create a rapid prototype to quickly learn and demonstrate the capabilities and value of the framework to the business. This can also generate excitement in the development team, particularly if the framework can enhance the productivity of developers and make their life easier.

 

The Frameworks I've Selected

The Spring Framework

I am a big fan of the Spring Framework. I believe it is really designed to support the need of developers from a productivity standpoint. In addition to dependency injection (DI), Aspect Oriented Programming (AOP), and Spring MVC, I like the Spring Data repository abstraction for JPA, MongoDB, Neo4J, and Hadoop. Spring supports Polyglot Persistence and Big Data today. I use Spring Roo for rapid application development and this allows me to focus on modeling the domain. I use the Roo scaffolding feature to generate a lot of Spring configuration and Java code for the domain, repository (Roo supports JPA and MongDB), service, and web layers (Roo supports Spring MVC, JSF, and GWT). Spring also support for unit and integration testing with the recent release of Spring MVC Test.

I use Spring Security which allows me to use AOP and annotations to secure methods and supports advanced features like Remenber Me and regular expressions for URLs. I think that JAAS is too low-level. Spring Security allows me to meet all OWASP Top Ten requirements (see my previous post entitled  Application-Level Security in Health IT Systems: A Roadmap).

Spring Social makes it easy to connect a Spring application to social network sites like Facebook, Twitter, and LinkedIn using the OAuth2 protocol. From a tooling standpoint, Spring STS supports many Spring features and I can deploy directly to Cloud Foundry from Spring STS. I look forward to evaluating Grails and the Play Framework which use convention over configuration and are built on Groovy and Scala respectively.

Thymeleaf, Twitter Boostrap, and JQuery

I use Twitter Boostrap because it is based on HTML5, CSS3, JQuery, LESS, and also supports a Responsive Web Design (RWD) approach. The size of the components library and the community is quite impressive.

Thymeleaf is an HTML5 templating engine and a replacement for traditional JSP. It is well integrated with Spring MVC and supports a clear division of labor between back-end and front-end developers. Twitter Boostrap and Thymeleaf work well together.

AngularJS

For Single Page Applications (SPA) my definitive choice is AngularJS. It provides everything I need including a clean MVC pattern implementation, directives, view routing, Deep Linking (for bookmarking), dependency injection, two-way databinding, and BDD-style unit testing with Jasmine. AngularJS has its own dedicated debugging tool called Batarang. There are also several learning resources (including books) on AngularJS.

Check this page comparing the performance of AngulaJS vs. KnockoutJS. This is a survey of the popularity of  Top JavaScript MVC Frameworks.

 

D3.js 

D3.js is my favorite for data visualization in data-intensive applications. It is based on HTML5, SVG, and Javascript. For simple charting and plotting, I use jqPlot which is based on JQuery. See my previous post entitled Visual Analytics for Clinical Decision Making.

 

R 

I use R for statistical computing, data analysis, and predictive analytics. See my previous post entitled Statistical Computing and Data Mining with R.

Development Tools

My development tools include: Git (Distributed Version Control), Maven or Gradle (build), Jenkins (Continuous Integration), Artifactory (Repository Manager), and Sonar (source code quality management). My testing toolkit includes Mockito, DBUnit, Cucumber JVM, JMeter, and Selenium.

Statistical Computing and Machine Learning with R

The use of predictive risk models for personalized medicine is becoming a common practice in healthcare delivery. These models can predict the health risk of patients based on their individual health profiles. Examples include models for predicting breast cancer, stroke, cardiovascular disease, Alzheimer's disease, chronic kidney disease, diabetes, hypertension, and operative mortality for patients undergoing cardiac surgery. These predictive models are created through data analysis using statistical computing.

Predictive risk modeling can be used to identity at-risk populations and provide them with pro-active care including early screening and prevention. For example, predictive risk modeling can help identify patients at risk of hospital re-admission, an important Accountable Care Organization (ACO) quality measure.

Another important challenge in healthcare is to discover what works and what does not work in clinical practice. Comparative Effectiveness Research (CER), an emerging trend in Evidence Based Practice (EBP), has been defined by the Federal Coordinating Council for CER as "the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat, and monitor health conditions in 'real world' settings."

Despite their inherent methodological challenges (lack of randomization leading to possible bias and confounding), observational studies (using real world clinical data) are increasingly recognized as complementary to Randomized Control Trials (RCTs) and an important tool in clinical decision making and health policy.

Statistical Computing and Machine Learning are essential components of intelligent health IT systems. Over the last few years, the free and open source R Project for Statistical Computing has emerged as one the most popular tools for data analysis. This poll by kdnuggets.com shows the breakdown in popularity of various data mining and analytic tools.

R supports several Machine Learning algorithms including:

• Nearest Neighbor
• Naive Bayes
• Decision Trees
• Logistic Regression
• Neural Networks
• Support Vector Machines
• Association Rules
• k-Means Clustering

A technique called "Ensemble Methods" which consists in combining multiple models into one can be used to achieve a higher level of accuracy than its components. There are also R packages for niche methods like the Latent Class Causal Analysis (LCCA) Package for R. LCA is used in behavioral health research.

The following are very useful resources for doing statistical computing and data mining with R:
 

• RStudio: an Integrated Development Environment (IDE) for R


• ggplot2: statistical graphics and plotting system for R


• sqldf: a package for manipulating R data frames using SQL


• RMySQL: R interface to the MySQL database


• RMongo: MongoDB Database interface for R
  


• RHIPE: Big Data analysis using R and Hadoop. RHIPE stands for R and Hadoop Integrated Programming Environment. This approach is referred to as D&R (Divide and Recombine) Analysis of Large Complex Data (see this tech report on D&R from the RHIPE team)


• RHadoop:  Big Data analysis using R and Hadoop. This tool provides Hadoop MapReduce functionality in R


• Rattle: A Graphical User Interface for Data Mining using R. This tool can export predictive models in Predictive Model Markup Language (PMML) format.

Automated Clinical Question Answering: The Next Frontier in Healthcare Informatics

In a previous post, I predicted that 2013 will be the year Intelligent Health IT Systems (iHIT) go mainstream.  I based my prediction on a number of factors, notably the transformation of healthcare to a value-based delivery system driven by the latest scientific evidence (evidence-based practice and practice-based evidence).

Last week, IBM together with health insurer WellPoint Inc., and New York’s Memorial Sloan-Kettering Cancer Center announced the commercialization of Watson (the supercomputer which beat human champions in "Jeopardy!" on February 16, 2011) for question answering (QA) in the clinical domain. The following are some interesting facts released by IBM as part of this announcement:

• The supercomputer has ingested 1,500 lung cancer cases from Sloan-Kettering records, plus 2 million pages of text from journals, textbooks and treatment guidelines. This is what I called Big Data in medicine.
• In 2012, Watson became 240 percent faster and 75 percent smaller so it can run on a single server. No surprise here and I expect this trend to continue.

The following YouTube video entitled Oncology Diagnosis and Treatment explains how IBM envisions using Watson for Clinical Question Answering (CQA):

The User Experience in the Watson Demo

 

• Clinical questions can be posed in natural language (spoken or typed in by the clinician using a keyboard).
• The sources used for answering clinical questions include both structured (EMR databases) and unstructured information (journal articles, clinical guidelines, etc.).
• Personalized medicine: the proposed interventions are driven by the data in the patient's medical record and the system can prompt the clinician for additional information on the patient if necessary. The displayed evidence and recommendations are updated to reflect changes in the patient's clinical data.
• Human Factors: the clinician is always in the loop. She can ask Watson how it arrives at a specific care recommendation and can even remove a specific evidence (if deemed irrelevant or not appropriate).
• The use of confidence scoring and evidence highlighting.
• Patient-centeredness and shared decision making: the treatment plans take into account the values, goals, and wishes of the patient (patient preferences). Treatment options are discussed with the patient.
• Comparative effectiveness is used to compare the benefits and harms of different interventions.
• Information is displayed using data visualization (dashboard) to help meet key performance indicators in the context of a value-based payment model.

The Science Behind Watson

The real question is how do we make intelligent health IT systems like Watson widely available to all patients. A landmark report published by the Institute of Medicine in 2001 and titled Crossing the Quality Chasm - A New Health System for the 21st Century contained the following recommendation:

Patients should receive care based on the best available scientific knowledge. Care should not vary illogically from clinician to clinician or from place to place.

For the scientifically (and Artificial Intelligence) inclined, the following are some pointers on the science behind Watson:

• The AI Behind Watson - The Technical Article
• Building Watson: An Overview of the DeepQA Project
• Unstructured Information Management (The IBM Journal of Research and Development)
• Semantic Web Technology in Watson.

The picture below represents a high level architecture of Watson (click on the image to enlarge it).

AskHermes and MiPACQ

IBM Watson is not the only effort to develop automated CQA capabilities.  Some earlier CQA efforts used the PICO framework (Problem/Population, Intervention, Comparison, Outcome) to facilitate processing. More recent efforts have focused on the use of clinical questions posed in natural language.

AskHermes (Help clinicians to Extract and aRrticulate Multimedia information for answering clinical quEstionS) allows clinicians to enter questions in natural language and uses the following unstructured information sources: MEDLINE abstracts, PubMed Central full-text articles, eMedicine documents, clinical guidelines, and Wikipedia articles.

The processing pipeline in AskHermes includes the following: Question Analysis, Related Questions Extraction, Information Retrieval, Summarization and Answer Presentation. AskHermes performs question classification using MMTx (MetaMap Technology Transfer) to map keywords to UMLS concepts  and semantic types. Classification is also achieved through supervised machine learning algorithms such as Support Vector Machine (SVM) and conditional random fields (CFRs). Summarization and answer presentation are based on clustering techniques.

MiPACQ (Multi-source Integrated Platform for Answering Clinical Questions) is based on Natural Language Processing (NLP) and Information Retrieval (IR) and utilizes data sources such as Electronic Medical Record (EMR) databases and online medical encyclopedia like Medpedia. MiPACQ uses a processing pipeline based on UIMA (Unstructured Information Management Architecture) and machine learning-based as well as rule-based scoring. NLP capabilities are provided by ClearTK and cTakes (clinical Text Analysis and Knowledge Extraction System).

The Road Ahead

Automated Clinical Question Answering (CQA) is really hard. However, that is the future of computing: intelligent machines we can have meaningful conversations with. CQA is a multidisciplinary field which combines disciplines like statistical computing, information retrieval, natural language processing, machine learning, rule engines, semantic web technologies, knowledge representation and reasoning, visual analytics, and massively parallel computing. There are several open source projects that provide the building blocks. Many EHR software today are glorified data entry systems. We need to move to the next level and that will require technical leadership.

Visual Analytics for Clinical Decision Making

In my last post, I talked about the era of Big Data in medicine, Evidence-Based Practice (EBP),  Practice-Based Evidence (PBE), and the need for a human-centered approach to building intelligent health IT (iHIT) systems. In this post, I discuss Visual Analytics, an emerging discipline in Data Science. In a report titled "Illuminating the Path: The R&D Agenda for Visual Analytics" published in 2004 by the National Visualization and Analytics Center (NVAC), Visual Analytics is defined as "the science of analytical reasoning facilitated by visual interactive interfaces."

The goal of Visual Analytics is to obtain deep insight for effective understanding, reasoning, and decision making through the visual exploration of massive, complex, and often ambiguous data. As a multidisciplinary field, Visual Analytics combines several disciplines such as human perception and cognition, interactive graphic design, statistical computing, data mining, spatio-temporal data analysis, and even art.

In his book titled "Beautiful Evidence", Edward Tufte illustrates the fundamental principles of analytical design by using Charles Minard's famous map known as "Carte figurative des pertes successives en hommes de l'Armée Française dans la campagne de Russie 1812-1813" (Figurative Map of the successive losses in men of the French Army in the Russian Campaign 1812-1813). The map is a dramatic account of the heavy losses of the french army during Napoleon's Russian campaign of 1812. Edward Tuffe calls the map the "best statistical graphics ever". Click on the image below to enlarge it.

Visual Analytics is also an emerging discipline in healthcare informatics. For example, similar to Minard's map of the Russian Campaign of 1812-1813, Visual Analytics can help in comparing different interventions and care pathways and their respective clinical outcomes over a certain period of time through the vivid showing of causes, variables, comparisons, and explanations. This approach contrasts with the traditional display of clinical data in table rows that is so common in electronic health record (EHR) systems interfaces.

Another Visual Analytics technique called Visual Cluster Analysis can be particularly helpful in Comparative Effectiveness in clinical care settings where the goal is to compare the benefits and harms of different interventions for different subgroups (groups of patients sharing similar clinical characteristics such as age, gender, race, genetic profile, and comorbidities). Given a specific patient, Visual Cluster Analysis can help the clinician visually explore what works and what doesn't work for "similar patients".

You can find interesting examples of research projects and implementations in the proceedings of the Visual Analytics in Healthcare Workshop which has been held in conjunction with the IEEE VisWeek for the past three years. The 2013 Visual Analytics in Healthcare Summit (VHAC 2013) will be held in conjunction with the AMIA 2013 conference in Washington DC. There are a number of open source toolkits that can be used to implement Visual Analytics. Some of them are based on open web standards such as HTML5, CSS3, SVG, and Javascript. My favorite is D3.js. DC.js and Crossfilter are built on top of D3.js and facilitate the creation of interactive visualization of multivariate datasets in the browser.

Prediction for 2013: Intelligent Health IT Systems (iHIT) Go Mainstream

iHIT systems represent an evolution of clinical decision support (CDS) systems. Traditionally, CDS systems have provided functionalities such as Alerts and Reminders, Order Sets, Infobuttons, and Documentation Templates. iHIT systems go beyond these basic functionalities and are poised to go mainstream in 2013. This evolution is enabled by recent developments in both computing and healthcare. Notably in computing:

• The emergence of Big Data and massively parallel computing platforms like Hadoop.
• The entrance of the following disciplines into the mainstream of computing: Machine Learning (a branch of Artificial Intelligence), Statistical Computing, Visual Analytics, Natural Language Processing, Information Retrieval, Rule engines, and Semantic Web Technologies (like RDF, OWL, SPARQL, and SWRL). These disciplines have been around for many years, but have been largely confined into Academia, very large organizations, and niche markets.
• The availability of open source tools, platforms, and resources to support the technologies mentioned above. Examples include: R (a statistical engine), Apache Hadoop, Apache Mahout, Apache Jena, Apache Stanbol, Apache OpenNLP, and Apache UIMA. The number of books, courses, and conferences dedicated to these topics has increased dramatically over the last two years signalling an entrance into the mainstream.

In addition, the healthcare industry itself is currently going through a significant transformation from a business model based on the number of patients treated to a value-based payment model. The Accountable Care Organization (ACO) is an example of this new model. This model puts an increased emphasis on meeting certain quality and performance metrics driven by the latest scientific evidence (this is called Evidence Based Practice or EBP).

Although very costly, Randomized Control Trials (RCTs) are considered the strongest form of evidence in EBP. Despite their inherent methodological challenges (lack of randomization leading to possible bias and confounding), observational studies (using real world data) are increasingly recognized as complementary to RCTs and an important tool in clinical decision making and health policy. According to a report titled "Clinical Practice Guidelines (CPGs) We Can Trust"  published by the Institute Of Medicine (IoM):

"Randomized trials commonly have an under representation of important subgroups, including those with comorbidities, older persons, racial and ethnic minorities, and low-income, less educated, or low-literacy patients."

Investments into Comparative Effectiveness Research (CER) are increasing as well. CER, an emerging trend in Evidence Based Practice (EBP), has been defined by the Federal Coordinating Council for CER as "the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat and monitor health conditions in 'real world' settings." CER is important not only for discovering what works and what doesn't work in practice, but also for an informed shared decision making process between the patient and her provider.

The use of predictive risk models for personalized medicine is becoming a common practice. These models can predict the health risks of patients based on their individual health profiles (including genetic profiles). These models often take the form of logistic regression models. Examples include models for predicting cardiovascular disease, ICU mortality, and hospital readmission (an important ACO performance measure).

Thanks to the Meaningful Use incentive program, adoption of electronic health record (EHR) systems by providers is rapidly increasing. This translates into the availability of huge amount of EHR data which can be harvested to provide Practice Based Evidence (PBE) necessary to close the evidence loop. PBE is the key to a learning health system. The Institute of Medicine (IOM) released a report last year titled "Digital Infrastructure for the Learning Health System: The Foundation for Continuous Improvement in Health and Health Care". The report describes a learning health system as:

"...delivery of best practice guidance at the point of choice, continuous learning and feedback in both health and health care, and seamless, ongoing communication among participants, all facilitated through the application of IT."

Both EBP and PBE will require not only rigorous scientific methodologies, but also a computing platform suitable for the era of Big Data in medicine. As Williams Osler (1849-1919) famously said:

"Medicine is a science of uncertainty and an art of probability."

Lastly, to be successful, the emergence of iHIT systems will require a human-centered design approach. This will be facilitated by the use of techniques that can enhance human cognitive abilities. Examples are: Electronic Checklists (an approach that originates from the aviation industry and has been proven to save lives in healthcare delivery as well) and Visual Analytics.

Happy New Year to You and Your Family!