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      Using electronic health records for clinical pharmacology research: Challenges and considerations

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          Abstract

          Electronic health records (EHRs) contain a vast array of phenotypic data on large numbers of individuals, often collected over decades. Due to the wealth of information, EHR data have emerged as a powerful resource to make first discoveries and identify disparities in our healthcare system. While the number of EHR‐based studies has exploded in recent years, most of these studies are directed at associations with disease rather than pharmacotherapeutic outcomes, such as drug response or adverse drug reactions. This is largely due to challenges specific to deriving drug‐related phenotypes from the EHR. There is great potential for EHR‐based discovery in clinical pharmacology research, and there is a critical need to address specific challenges related to accurate and reproducible derivation of drug‐related phenotypes from the EHR. This review provides a detailed evaluation of challenges and considerations for deriving drug‐related data from EHRs. We provide an examination of EHR‐based computable phenotypes and discuss cutting‐edge approaches to map medication information for clinical pharmacology research, including medication‐based computable phenotypes and natural language processing. We also discuss additional considerations such as data structure, heterogeneity and missing data, rare phenotypes, and diversity within the EHR. By further understanding the complexities associated with conducting clinical pharmacology research using EHR‐based data, investigators will be better equipped to design thoughtful studies with more reproducible results. Progress in utilizing EHRs for clinical pharmacology research should lead to significant advances in our ability to understand differential drug response and predict adverse drug reactions.

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          Most cited references101

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          The “All of Us” Research Program

          (2019)
          Knowledge gained from observational cohort studies has dramatically advanced the prevention and treatment of diseases. Many of these cohorts, however, are small, lack diversity, or do not provide comprehensive phenotype data. The All of Us Research Program plans to enroll a diverse group of at least 1 million persons in the United States in order to accelerate biomedical research and improve health. The program aims to make the research results accessible to participants, and it is developing new approaches to generate, access, and make data broadly available to approved researchers. All of Us opened for enrollment in May 2018 and currently enrolls participants 18 years of age or older from a network of more than 340 recruitment sites. Elements of the program protocol include health questionnaires, electronic health records (EHRs), physical measurements, the use of digital health technology, and the collection and analysis of biospecimens. As of July 2019, more than 175,000 participants had contributed biospecimens. More than 80% of these participants are from groups that have been historically underrepresented in biomedical research. EHR data on more than 112,000 participants from 34 sites have been collected. The All of Us data repository should permit researchers to take into account individual differences in lifestyle, socioeconomic factors, environment, and biologic characteristics in order to advance precision diagnosis, prevention, and treatment.
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            Observational Health Data Sciences and Informatics (OHDSI): Opportunities for Observational Researchers.

            The vision of creating accessible, reliable clinical evidence by accessing the clincial experience of hundreds of millions of patients across the globe is a reality. Observational Health Data Sciences and Informatics (OHDSI) has built on learnings from the Observational Medical Outcomes Partnership to turn methods research and insights into a suite of applications and exploration tools that move the field closer to the ultimate goal of generating evidence about all aspects of healthcare to serve the needs of patients, clinicians and all other decision-makers around the world.
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              Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association

              Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. The antihypertensive drugs should be administered at maximum or maximally tolerated daily doses. RH also includes patients whose BP achieves target values on ≥4 antihypertensive medications. The diagnosis of RH requires assurance of antihypertensive medication adherence and exclusion of the "white-coat effect" (office BP above goal but out-of-office BP at or below target). The importance of RH is underscored by the associated risk of adverse outcomes compared with non-RH. This article is an updated American Heart Association scientific statement on the detection, evaluation, and management of RH. Once antihypertensive medication adherence is confirmed and out-of-office BP recordings exclude a white-coat effect, evaluation includes identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. Management of RH includes maximization of lifestyle interventions, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and, if BP remains elevated, stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower BP. If BP remains uncontrolled, referral to a hypertension specialist is advised.
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                Author and article information

                Contributors
                cmcdonough@cop.ufl.edu
                Journal
                Clin Transl Sci
                Clin Transl Sci
                10.1111/(ISSN)1752-8062
                CTS
                Clinical and Translational Science
                John Wiley and Sons Inc. (Hoboken )
                1752-8054
                1752-8062
                28 June 2024
                July 2024
                : 17
                : 7 ( doiID: 10.1111/cts.v17.7 )
                : e13871
                Affiliations
                [ 1 ] Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida Gainesville Florida USA
                [ 2 ] Department of Pharmacy Practice, College of Pharmacy Jazan University Jazan Saudi Arabia
                [ 3 ] Department of Biostatistics Vanderbilt University Medical Center Nashville Tennessee USA
                [ 4 ] Department of Pharmacy Practice and Science University of Arizona R. Ken Coit College of Pharmacy Tucson Arizona USA
                [ 5 ] Department of Pediatrics Vanderbilt University Medical Center (VUMC) Nashville Tennessee USA
                [ 6 ] Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology Case Western Reserve University Cleveland Ohio USA
                [ 7 ] Department of Genetics and Genome Sciences, Cleveland Institute for Computational Biology Case Western Reserve University Cleveland Ohio USA
                [ 8 ] Department of Biostatistics and Biomedical Informatics Vanderbilt University Medical Center Nashville Tennessee USA
                [ 9 ]Present address: All of US Research Program, National Institutes of Health Bethesda Maryland USA
                Author notes
                [*] [* ] Correspondence

                Caitrin W. McDonough, Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine, University of Florida, P.O. Box 100484, Gainesville, FL 32610‐0486, USA.

                Email: cmcdonough@ 123456cop.ufl.edu

                Author information
                https://orcid.org/0000-0002-9898-185X
                https://orcid.org/0000-0001-5001-3334
                https://orcid.org/0000-0003-2580-1405
                https://orcid.org/0000-0001-6393-7288
                Article
                CTS13871 CTS-2021-0317C
                10.1111/cts.13871
                11213823
                38943244
                7f5674b9-8eb6-4031-8958-a5aabcc98c9e
                © 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 21 May 2024
                : 19 March 2024
                : 24 May 2024
                Page count
                Figures: 0, Tables: 5, Pages: 17, Words: 12100
                Funding
                Funded by: NIH , doi 10.13039/100000002;
                Award ID: K01 HL141690
                Award ID: R03 HL172123
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                July 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.5 mode:remove_FC converted:29.06.2024

                Medicine
                Medicine

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