Case Studies for Overcoming Challenges in Using Big Data in Cancer.

The analysis of big healthcare data has enormous potential as a tool for advancing oncology drug development and patient treatment, particularly in the context of precision medicine. However, there are challenges in organizing, sharing, integrating, and making these data readily accessible to the research community. This review presents five case studies illustrating various successful approaches to addressing such challenges.

Challenges to Using Big Data in Cancer.

Big data in healthcare can enable unprecedented understanding of diseases and their treatment, particularly in oncology. These data may include electronic health records, medical imaging, genomic sequencing, payor records, and data from pharmaceutical research, wearables, and medical devices. The ability to combine datasets and use data across many analyses is critical to the successful use of big data and is a concern for those who generate and use the data.

Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events.

Background: Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.

Methods: In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg.

Design of a pragmatic clinical trial embedded in the Electronic Health Record: The VA's Diuretic Comparison Project.

Background: Recent US guidelines recommend chlorthalidone over other thiazide-type diuretics for the treatment of hypertension based on its long half-life and proven ability to reduce CVD events. Despite recommendations most clinicians prescribe hydrochlorothiazide (HCTZ) over chlorthalidone (CTD). No randomized controlled data exist comparing these two diuretics on cardiovascular outcomes.

Creatinine standardization: a key consideration in evaluating whole blood creatinine monitoring systems for CKD screening.

Early detection of CKD using point of care creatinine and eGFR testing improves patient management outcomes. We undertook a field study to evaluate the use of a whole blood creatinine/eGFR device to screen a rural Nicaraguan population to determine the variability between creatinine methods and specimen types. All specimens including capillary and venous dried blood spots (DBS) were tested with an isotope dilution liquid chromatography mass spectrometry (ID-LCMS) gold standard method.

Prevalence and Risk Factors for CKD in the General Population of Southwestern Nicaragua.

Background: Studies have described Mesoamerican nephropathy among agricultural workers of El Salvador and northwestern Nicaragua. Data on prevalence and risk factors for CKD beyond agricultural workers and in other regions in Nicaragua are sparse.

Methods: We recruited participants from 32 randomly selected communities in the Department of Rivas's ten municipalities in two phases.

Streamlining cardiovascular clinical trials to improve efficiency and generalisability.

Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected.

Identification of Acute Decompensated Heart Failure Hospitalizations Using Administrative Data.

Hospitalization for acute decompensated heart failure (ADHF) is an important outcome in clinical trials and heart failure registries; however, the optimal strategy to identify these hospitalizations using International Classification of Diseases, Ninth Revision (ICD-9) codes is uncertain. We sought to identify diagnostic codes that improve ascertainment of ADHF hospitalizations. Heart failure-related ICD-9 principal discharge codes were used to identify 2,202 hospitalizations within the Minneapolis Veterans Affairs Medical Center from 2009 to 2014.

The Rivas Cohort Study: design and baseline characteristics of a Nicaraguan cohort.

Background: A lack of advanced healthcare information systems and validated scientific cohorts in Nicaragua makes it difficult to estimate disease prevalences and other public health statistics. Although there is concern of an "epidemic" of chronic kidney disease (CKD) in this country, statistics regarding its magnitude are derived from only a small number of non-representative studies. Budgetary constraints and the logistical problems of maintaining a study cohort make longitudinal studies difficult.

The VA Point-of-Care Precision Oncology Program: Balancing Access with Rapid Learning in Molecular Cancer Medicine.

The Department of Veterans Affairs (VA) recognized the need to balance patient-centered care with responsible creation of generalizable knowledge on the effectiveness of molecular medicine tools. Embracing the principles of the rapid learning health-care system, a new clinical program called the Precision Oncology Program (POP) was created in New England. The POP integrates generalized knowledge about molecular medicine in cancer with a database of observations from previously treated veterans.

Implementation of a Precision Oncology Program as an Exemplar of a Learning Health Care System in the VA.

The program determines and disseminates precision oncology best practices; enhances patient and provider engagement; and fosters collaboration among the VA, National Cancer Institute, academia, other health care systems, and industry to provide cancer patients with access to clinical trial participation.

Million Veteran Program: A mega-biobank to study genetic influences on health and disease.

Objective: To describe the design and ongoing conduct of the Million Veteran Program (MVP), as an observational cohort study and mega-biobank in the Department of Veterans Affairs (VA) health care system.

Study Design And Setting: Data are being collected from participants using questionnaires, the VA electronic health record, and a blood sample for genomic and other testing. Several ongoing projects are linked to MVP, both as peer-reviewed research studies and as activities to help develop an infrastructure for future, broad-based research uses.

Chronic kidney disease prevalence in Rivas, Nicaragua: use of a field device for creatinine measurement.

Objective: An epidemic of chronic kidney disease (CKD) has been identified in Pacific coastal regions of Central America, and screening in the field in these low income countries remains logistically problematic. We tested the performance characteristics of a point of care creatinine analyzer compared to standardized serum creatinine measurements.

Methods: Measurements were conducted in 100 persons from a local health center (n=34) and hospital (n=66) in Rivas, Nicaragua using both a point-of-care analyzer (StatSensor Xpress, Nova Biomedical) and serum creatinine by Jaffe kinetic method with a Roche Cobas Integra 400 analyzer.

Veterans Healthcare Administration providers' attitudes and perceptions regarding pragmatic trials embedded at the point of care.

Background The Veterans Healthcare Administration (VA) is implementing an adaptation of a pragmatic trial program, Point of Care Research (POC-R). The goal of POC-R is to embed research into clinical practice, contributing to a Learning Healthcare System. Provider acceptance and participation in POC-R is essential to its successful implementation.

A comprehensive care management program to prevent chronic obstructive pulmonary disease hospitalizations: a randomized, controlled trial.

Background: Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes.

Objective: To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization.

Design: A randomized, controlled trial comparing CCMP with guideline-based usual care.

Measuring use of evidence based psychotherapy for posttraumatic stress disorder.

To improve methods of estimating use of evidence-based psychotherapy for posttraumatic stress disorder in the Veteran's health administration, we evaluated administrative data and note text for patients newly enrolling in six VHA outpatient PTSD clinics in New England during the 2010 fiscal year (n = 1,924). Using natural language processing, we developed machine learning algorithms that mimic human raters in classifying note text. We met our targets for algorithm performance as measured by precision, recall, and F-measure.

Implementation of the Department of Veterans Affairs' first point-of-care clinical trial.

Objectives: The Massachusetts Veterans Epidemiology Research and Information Center in collaboration with the Stanford Center for Innovative Study Design set out to test the feasibility of a new method of evidence generation. The first pilot of a point-of-care clinical trial (POCCT), adding randomization and other study processes to an electronic medical record (EMR) system, was launched to compare the effectiveness of two insulin regimens.

Materials And Methods: Existing functionalities of the Veterans Affairs (VA) computerized patient record system (CPRS)/veterans health information systems and technology architecture (VISTA) were modified to support the activities of a randomized controlled trial including enrolment, randomization, and longitudinal data collection.

Risk of community-acquired pneumonia in veteran patients to whom proton pump inhibitors were dispensed.

Background: Observational studies linking proton pump inhibitor (PPI) exposure with community-acquired pneumonia (CAP) have reported either modest or no associations. Accordingly, we studied PPI exposure and CAP in veteran patients, using a retrospective, nested case-control design.

Methods: From linked pharmacy and administrative databases of the New England Veterans Healthcare System, we identified 71985 outpatients newly prescribed PPIs between 1998 and 2007; 1544 patients met criteria for CAP subsequent to PPI initiation; 15440 controls were matched through risk-set sampling by age and time under observation.

Automated concept-level information extraction to reduce the need for custom software and rules development.

Objective: Despite at least 40 years of promising empirical performance, very few clinical natural language processing (NLP) or information extraction systems currently contribute to medical science or care. The authors address this gap by reducing the need for custom software and rules development with a graphical user interface-driven, highly generalizable approach to concept-level retrieval.

Materials And Methods: A 'learn by example' approach combines features derived from open-source NLP pipelines with open-source machine learning classifiers to automatically and iteratively evaluate top-performing configurations.

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen.

Background: Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care.