Creation of a Multicenter Pediatric Inpatient Data Repository Derived from Electronic Health Records

Christoph P. Hornik; Andrew M. Atz; Catherine Bendel; Francis Chan; Kevin Downes; Robert Grundmeier; Ben Fogel; Debbie Gipson; Matthew Laughon; Michael Miller; Michael Smith; Chad Livingston; Cindy Kluchar; Anne Heath; Chanda Jarrett; Brian McKerlie; Hetalkumar Patel; Christina Hunter; on behalf of the Best Pharmaceuticals for Children Act–Pediatric Trials Network

doi:10.1055/s-0039-1688477

Applied Clinical Informatics, Table of Contents

Appl Clin Inform 2019; 10(02): 307-315
DOI: 10.1055/s-0039-1688477

Case Report

Georg Thieme Verlag KG Stuttgart · New York

Creation of a Multicenter Pediatric Inpatient Data Repository Derived from Electronic Health Records

Christoph P. Hornik

¹Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States

,

Andrew M. Atz

²Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, United States

,

Catherine Bendel

³Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, United States

,

Francis Chan

⁴Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California, United States

,

Kevin Downes

⁵Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, United States

,

Robert Grundmeier

⁵Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, United States

,

Ben Fogel

⁶Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

,

Debbie Gipson

⁷Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor, Michigan, United States

,

Matthew Laughon

⁸Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

,

Michael Miller

⁹Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States

,

Michael Smith

¹⁰Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, United States

¹¹Division of Pediatric Infectious Diseases, Duke University School of Medicine, Durham North Carolina, United States

,

Chad Livingston

¹Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States

,

Cindy Kluchar

¹Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States

,

Anne Heath

¹Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States

,

Chanda Jarrett

¹Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States

,

Brian McKerlie

¹Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States

,

Hetalkumar Patel

¹Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States

,

Christina Hunter

¹Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States

,

on behalf of the Best Pharmaceuticals for Children Act–Pediatric Trials Network

› Author Affiliations

Abstract

Background Integration of electronic health records (EHRs) data across sites and access to that data remain limited.

Objective We developed an EHR-based pediatric inpatient repository using nine U.S. centers from the National Institute of Child Health and Human Development Pediatric Trials Network.

Methods A data model encompassing 147 mandatory and 99 optional elements was developed to provide an EHR data extract of all inpatient encounters from patients <17 years of age discharged between January 6, 2013 and June 30, 2017. Sites received instructions on extractions, transformation, testing, and transmission to the coordinating center.

Results We generated 177 staging reports to process all nine sites' 147 mandatory and 99 optional data elements to the repository. Based on 520 prespecified criteria, all sites achieved 0% errors and <2% warnings. The repository includes 386,159 inpatient encounters from 264,709 children to support study design and conduct of future trials in children.

Conclusion Our EHR-based data repository of pediatric inpatient encounters utilized a customized data model heavily influenced by the PCORnet format, site-based data mapping, a comprehensive set of data testing rules, and an iterative process of data submission. The common data model, site-based extraction, and technical expertise were key to our success. Data from this repository will be used in support of Pediatric Trials Network studies and the labeling of drugs and devices for children.

Keywords

pediatric clinical trials - electronic heath record reuse - NICHD Pediatric Trials Network - inpatient repository - data extraction

Full Text

References

References
1 Park HA. President's Statement. Yearb Med Inform 2017; 26 (01) 1-2
2 Issa NT, Byers SW, Dakshanamurthy S. Big data: the next frontier for innovation in therapeutics and healthcare. Expert Rev Clin Pharmacol 2014; 7 (03) 293-298
3 Margolis R, Derr L, Dunn M. , et al. The National Institutes of Health's Big Data to Knowledge (BD2K) initiative: capitalizing on biomedical big data. J Am Med Inform Assoc 2014; 21 (06) 957-958
4 Ross MK, Wei W, Ohno-Machado L. “Big data” and the electronic health record. Yearb Med Inform 2014; 9: 97-104
5 Evans RS. Electronic health records: then, now, and in the future. Yearb Med Inform 2016; (Suppl. 01) S48-S61
6 Weng C, Kahn MG. Clinical research informatics for big data and precision medicine. Yearb Med Inform 2016; 25 (01) 211-218
7 Elliott JH, Grimshaw J, Altman R. , et al. Informatics: make sense of health data. Nature 2015; 527 (7576): 31-32
8 Sutherland SM, Kaelber DC, Downing NL, Goel VV, Longhurst CA. Electronic health record-enabled research in children using the electronic health record for clinical discovery. Pediatr Clin North Am 2016; 63 (02) 251-268
9 Sward KA, Rubin S, Jenkins TL, Newth CJ, Dean JM. ; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN). Case study: semantic annotation of a pediatric critical care research study. Comput Inform Nurs 2016; 34 (03) 101-104
10 Zhao J, Henriksson A, Asker L, Boström H. Predictive modeling of structured electronic health records for adverse drug event detection. BMC Med Inform Decis Mak 2015; 15 (Suppl. 04) S1
11 Silverstein JM, Roe ED, Munir KM. , et al. Use of electronic health records to characterize a rare disease in the U.S.: treatment, comorbidities, and follow-up trends among patients with a confirmed diagnosis of acromegaly. Endocr Pract 2018; 24 (06) 517-526
12 Liu F, Jagannatha A, Yu H. Towards drug safety surveillance and pharmacovigilance: current progress in detecting medication and adverse drug events from electronic health records. Drug Saf 2019; 42 (01) 95-97
13 Imatoh T, Sai K, Takeyama M. , et al. Identification of risk factors and development of detection algorithm for denosumab-induced hypocalcaemia. J Clin Pharm Ther 2019; 44 (01) 62-68
14 Laughon MM, Benjamin Jr DK. Mechanisms to provide safe and effective drugs for children. Pediatrics 2014; 134 (02) e562-e563
15 England A, Wade K, Smith PB, Berezny K, Laughon M. ; Best Pharmaceuticals for Children Act — Pediatric Trials Network Administrative Core Committee. Optimizing operational efficiencies in early phase trials: the Pediatric Trials Network experience. Contemp Clin Trials 2016; 47: 376-382
16 Laughon MM, Benjamin Jr DK, Capparelli EV. , et al. Innovative clinical trial design for pediatric therapeutics. Expert Rev Clin Pharmacol 2011; 4 (05) 643-652
17 Hornik CP, Benjamin Jr DK, Smith PB. , et al; Best Pharmaceuticals for Children Act—Pediatric Trials Network. Electronic health records and pharmacokinetic modeling to assess the relationship between ampicillin exposure and seizure risk in neonates. J Pediatr 2016; 178: 125-129.e1
18 Hornik CP, Chu PY, Li JS, Clark RH, Smith PB, Hill KD. Comparative effectiveness of digoxin and propranolol for supraventricular tachycardia in infants. Pediatr Crit Care Med 2014; 15 (09) 839-845
19 Testoni D, Hornik CP, Neely ML. , et al; Best Pharmaceuticals for Children Act — Pediatric Trials Network Administrative Core Committee. Safety of octreotide in hospitalized infants. Early Hum Dev 2015; 91 (07) 387-392
20 Zimmerman KO, Hornik CP, Ku L. , et al. Sedatives and analgesics given to infants in neonatal intensive care units at the end of life. J Pediatr 2015; 167 (02) 299-304
21 Autmizguine J, Hornik CP, Benjamin Jr DK. , et al; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee. Anaerobic antimicrobial therapy after necrotizing enterocolitis in VLBW infants. Pediatrics 2015; 135 (01) e117-e125
22 Fiks AG, Grundmeier RW, Steffes J. , et al; Comparative Effectiveness Research Through Collaborative Electronic Reporting (CER2) Consortium. Comparative effectiveness research through a collaborative electronic reporting consortium. Pediatrics 2015; 136 (01) e215-e224
23 FHIR R4. A Standard for Health Care Data Exchange. Available at: http://www.hl7.org/fhir/index.html . Accessed February 1, 2019
24 HL7 Standards-Section 3: Clinical and Administrative Domains. Available at: http://www.hl7.org/implement/standards/product_section.cfm?section=3 . Accessed February 1, 2019
25 CDISC. Biomedical Research Integrated Domain Group (BRIDG) Model. Available at: https://www.cdisc.org/standards/domain-information-module/bridg . Accessed February 1, 2019
26 PCORnet Common Data Model (CDM) Specification.Version 2.0. Available at: http://pcornet.org/wp-content/uploads/2015/03/2015-02-27-PCORnet-Common-Data-Model-v2-0-RELEASE.pdf . Accessed February 1, 2019
27 U.S. National Library of Medicine. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/resources/download . Accessed February 1, 2019
28 Selby JV, Lipstein SH. PCORI at 3 years--progress, lessons, and plans. N Engl J Med 2014; 370 (07) 592-595
29 Zhou X, Murugesan S, Bhullar H. , et al. An evaluation of the THIN database in the OMOP Common Data Model for active drug safety surveillance. Drug Saf 2013; 36 (02) 119-134
30 Xu Y, Zhou X, Suehs BT. , et al. A comparative assessment of Observational Medical Outcomes Partnership and Mini-Sentinel common data models and analytics: implications for active drug safety surveillance. Drug Saf 2015; 38 (08) 749-765
31 Stang PE, Ryan PB, Racoosin JA. , et al. Advancing the science for active surveillance: rationale and design for the Observational Medical Outcomes Partnership. Ann Intern Med 2010; 153 (09) 600-606
32 PCORnet. PCORnet Coordinating Center. Available at: https://pcornet.org/about-pcornet/pcornet-coordinating-center/ . Accessed February 6, 2019
33 National Institute of Standards and Technology. Federal Information Security Management Act (FISMA) Implementation Project. Available at: https://www.nist.gov/programs-projects/federal-information-security-management-act-fisma-implementation-project . Accessed February 6, 2019
34 Antman EM, Benjamin EJ, Harrington RA. , et al; American Heart Association Data Sharing Summit Attendees. Acquisition, analysis, and sharing of data in 2015 and beyond: a survey of the landscape: a conference report from the American Heart Association Data Summit 2015. J Am Heart Assoc 2015; 4 (11) e002810
35 Janke AT, Overbeek DL, Kocher KE, Levy PD. Exploring the potential of predictive analytics and big data in emergency care. Ann Emerg Med 2016; 67 (02) 227-236
36 Khoury MJ. Planning for the future of epidemiology in the era of big data and precision medicine. Am J Epidemiol 2015; 182 (12) 977-979
37 Kim J. Big data, health informatics, and the future of cardiovascular medicine. J Am Coll Cardiol 2017; 69 (07) 899-902
38 Sutherland SM, Goldstein SL, Bagshaw SM. Acute kidney injury and big data. Contrib Nephrol 2018; 193: 55-67
39 Deakyne Davies SJ, Grundmeier RW, Campos DA. , et al; Pediatric Emergency Care Applied Research Network. The Pediatric Emergency Care Applied Research Network Registry: a multicenter electronic health record registry of pediatric emergency care. Appl Clin Inform 2018; 9 (02) 366-376
40 Deans KJ, Sabihi S, Forrest CB. Learning health systems. Semin Pediatr Surg 2018; 27 (06) 375-378
41 Forrest CB, Margolis P, Seid M, Colletti RB. PEDSnet: how a prototype pediatric learning health system is being expanded into a national network. Health Aff (Millwood) 2014; 33 (07) 1171-1177
42 Forrest CB, Margolis PA, Bailey LC. , et al. PEDSnet: a national pediatric learning health system. J Am Med Inform Assoc 2014; 21 (04) 602-606
43 Khare R, Utidjian L, Ruth BJ. , et al. A longitudinal analysis of data quality in a large pediatric data research network. J Am Med Inform Assoc 2017; 24 (06) 1072-1079
44 Hemingway H, Asselbergs FW, Danesh J. , et al; Innovative Medicines Initiative 2nd programme, Big Data for Better Outcomes, BigData@Heart Consortium of 20 academic and industry partners including ESC. Big data from electronic health records for early and late translational cardiovascular research: challenges and potential. Eur Heart J 2018; 39 (16) 1481-1495
45 Weng C. Optimizing clinical research participant selection with informatics. Trends Pharmacol Sci 2015; 36 (11) 706-709
46 De Moor G, Sundgren M, Kalra D. , et al. Using electronic health records for clinical research: the case of the EHR4CR project. J Biomed Inform 2015; 53: 162-173
47 Hernandez AF, Fleurence RL, Rothman RL. The ADAPTABLE Trial and PCORnet: shining light on a new research paradigm. Ann Intern Med 2015; 163 (08) 635-636
48 Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin Jr DK, Smith PB. ; Best Pharmaceuticals for Children Act—Pediatric Trials Network. Medication use in the neonatal intensive care unit. Am J Perinatol 2014; 31 (09) 811-821
49 Trembath A, Hornik CP, Clark R, Smith PB, Daniels J, Laughon M. ; Best Pharmaceuticals for Children Act—Pediatric Trials Network. Comparative effectiveness of surfactant preparations in premature infants. J Pediatr 2013; 163 (04) 955-60.e1
50 Ericson JE, Gostelow M, Autmizguine J. , et al; Pediatric Trials Network Executive Committee and Investigators. Safety of high-dose acyclovir in infants with suspected and confirmed neonatal herpes simplex virus infections. Pediatr Infect Dis J 2017; 36 (04) 369-373
51 Hornik CP, Herring AH, Benjamin Jr DK. , et al; Best Pharmaceuticals for Children Act-Pediatric Trials Network. Adverse events associated with meropenem versus imipenem/cilastatin therapy in a large retrospective cohort of hospitalized infants. Pediatr Infect Dis J 2013; 32 (07) 748-753
52 Autmizguine J, Benjamin Jr DK, Smith PB. , et al. Pharmacokinetic studies in infants using minimal-risk study designs. Curr Clin Pharmacol 2014; 9 (04) 350-358
53 Salerno S, Hornik CP, Cohen-Wolkowiez M. , et al; Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee. Use of population pharmacokinetics and electronic health records to assess piperacillin-tazobactam safety in infants. Pediatr Infect Dis J 2017; 36 (09) 855-859
54 Hornik CP, Onufrak NJ, Smith PB. , et al. Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants. Cardiol Young 2018; 28 (01) 85-92
55 Ku LC, Wu H, Greenberg RG. , et al. Use of therapeutic drug monitoring, electronic health record data, and pharmacokinetic modeling to determine the therapeutic index of phenytoin and lamotrigine. Ther Drug Monit 2016; 38 (06) 728-737
56 Ge S, Beechinor RJ, Hornik CP. , et al. External evaluation of a gentamicin infant population pharmacokinetic model using data from a national electronic health record database. Antimicrob Agents Chemother 2018; 62 (09) e00669-e18
57 Gliklich R, Dreyer N, Leavy M, Velentgas P, Khurana L. Standards in the conduct of registry studies for patient-centered outcomes research. Patient-Centered Outcomes Research Institute;March 15, 2012. Available at: https://www.pcori.org/assets/Standards-in-the-Conduct-of-Registry-Studies-for-Patient-Centered-Outcomes-Research.pdf . Accessed June 6, 2018
58 Leavy MB. Multinational registries: challenges and opportunities. Addendum to Registries for Evaluating Patient Outcomes: A User's Guide.3rd ed. Rockville, MD: Agency for Healthcare Research and Quality; 2018
59 Mack C, Su Z, Westreich D. Managing missing data in patient registries. Addendum to Registries for Evaluating Patient Outcomes: A User's Guide.3rd ed. Rockville, MD: Agency for Healthcare Research and Quality; 2018
60 Velupillai S, Mowery D, South BR, Kvist M, Dalianis H. Recent advances in clinical natural language processing in support of semantic analysis. Yearb Med Inform 2015; 10 (01) 183-193

Supplementary Material

Supplementary Material