Douglas MacFadden

The co-morbidity burden of children and young adults with autism spectrum disorders.

Objectives Use electronic health records Autism Spectrum Disorder (ASD) to assess the comorbidity burden of ASD in children and young adults. Study Design A retrospective prevalence study was performed using a distributed query system across three general hospitals and one pediatric hospital. Over 14,000 individuals under age 35 with ASD were characterized by their co-morbidities and conversely, the prevalence of ASD within these comorbidities was measured. The comorbidity prevalence of the younger (Age<18 years) and older (Age 18–34 years) individuals with ASD was compared. Results 19.44% of ASD patients had epilepsy as compared to 2.19% in the overall hospital population (95% confidence interval for difference in percentages 13.58–14.69%), 2.43% of ASD with schizophrenia vs. 0.24% in the hospital population (95% CI 1.89–2.39%), inflammatory bowel disease (IBD) 0.83% vs. 0.54% (95% CI 0.13–0.43%), bowel disorders (without IBD) 11.74% vs. 4.5% (95% CI 5.72–6.68%), CNS/cranial anomalies 12.45% vs. 1.19% (95% CI 9.41–10.38%), diabetes mellitus type I (DM1) 0.79% vs. 0.34% (95% CI 0.3–0.6%), muscular dystrophy 0.47% vs 0.05% (95% CI 0.26–0.49%), sleep disorders 1.12% vs. 0.14% (95% CI 0.79–1.14%). Autoimmune disorders (excluding DM1 and IBD) were not significantly different at 0.67% vs. 0.68% (95% CI −0.14-0.13%). Three of the studied comorbidities increased significantly when comparing ages 0–17 vs 18–34 with p<0.001: Schizophrenia (1.43% vs. 8.76%), diabetes mellitus type I (0.67% vs. 2.08%), IBD (0.68% vs. 1.99%) whereas sleeping disorders, bowel disorders (without IBD) and epilepsy did not change significantly. Conclusions The comorbidities of ASD encompass disease states that are significantly overrepresented in ASD with respect to even the patient populations of tertiary health centers. This burden of comorbidities goes well beyond those routinely managed in developmental medicine centers and requires broad multidisciplinary management that payors and providers will have to plan for.

The Shared Health Research Information Network (SHRINE): A Prototype Federated Query Tool for Clinical Data Repositories

The authors developed a prototype Shared Health Research Information Network (SHRINE) to identify the technical, regulatory, and political challenges of creating a federated query tool for clinical data repositories. Separate Institutional Review Boards (IRBs) at Harvards three largest affiliated health centers approved use of their data, and the Harvard Medical School IRB approved building a Query Aggregator Interface that can simultaneously send queries to each hospital and display aggregate counts of the number of matching patients. Our experience creating three local repositories using the open source Informatics for Integrating Biology and the Bedside (i2b2) platform can be used as a road map for other institutions. The authors are actively working with the IRBs and regulatory groups to develop procedures that will ultimately allow investigators to obtain identified patient data and biomaterials through SHRINE. This will guide us in creating a future technical architecture that is scalable to a national level, compliant with ethical guidelines, and protective of the interests of the participating hospitals.

SHRINE: Enabling Nationally Scalable Multi-Site Disease Studies

Results of medical research studies are often contradictory or cannot be reproduced. One reason is that there may not be enough patient subjects available for observation for a long enough time period. Another reason is that patient populations may vary considerably with respect to geographic and demographic boundaries thus limiting how broadly the results apply. Even when similar patient populations are pooled together from multiple locations, differences in medical treatment and record systems can limit which outcome measures can be commonly analyzed. In total, these differences in medical research settings can lead to differing conclusions or can even prevent some studies from starting. We thus sought to create a patient research system that could aggregate as many patient observations as possible from a large number of hospitals in a uniform way. We call this system the ‘Shared Health Research Information Network’, with the following properties: (1) reuse electronic health data from everyday clinical care for research purposes, (2) respect patient privacy and hospital autonomy, (3) aggregate patient populations across many hospitals to achieve statistically significant sample sizes that can be validated independently of a single research setting, (4) harmonize the observation facts recorded at each institution such that queries can be made across many hospitals in parallel, (5) scale to regional and national collaborations. The purpose of this report is to provide open source software for multi-site clinical studies and to report on early uses of this application. At this time SHRINE implementations have been used for multi-site studies of autism co-morbidity, juvenile idiopathic arthritis, peripartum cardiomyopathy, colorectal cancer, diabetes, and others. The wide range of study objectives and growing adoption suggest that SHRINE may be applicable beyond the research uses and participating hospitals named in this report.

Accrual to Clinical Trials (ACT): A Clinical and Translational Science Award Consortium Network

Abstract The Accrual to Clinical Trials (ACT) network is a federated network of sites from the National Clinical and Translational Science Award (CTSA) Consortium that has been created to significantly increase participant accrual to multi-site clinical trials. The ACT network represents an unprecedented collaboration among diverse CTSA sites. The network has created governance and regulatory frameworks and a common data model to harmonize electronic health record (EHR) data, and deployed a set of Informatics for Integrating Biology and the Bedside (i2b2) data repositories that are linked by the Shared Health Research Information Network (SHRINE) platform. It provides investigators the ability to query the network in real time and to obtain aggregate counts of patients who meet clinical trial inclusion and exclusion criteria from sites across the United States. The ACT network infrastructure provides a basis for cohort discovery and for developing new informatics tools to identify and recruit participants for multi-site clinical trials.