Diagnosing Adverse Drug Reactions Registry (DART)

DART Registry: Diagnosing Adverse Drug Reactions Registry

This multicenter Registry is to assess whether the use of pharmacogenomic data results in a meaningful change in a subject's drug or dose regimen. In addition, the Registry will evaluate the relationship between adverse drug reactions (ADR) and genotype and assess resource utilization (emergency department visits and hospitalizations) associated with ADR.

Study Overview

• Status: Unknown
• Conditions: Genetics of Drug Metabolism

• Study Type: Observational
• Enrollment (Anticipated): 250000

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Edwards Lake Medical Center
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Gerald Harris MD
    • Peoria, Arizona, United States, 85381
      • Holland Center for Family Health
    • Phoenix, Arizona, United States, 85032
      • AZ Pain Center
  • California
    • Los Angeles, California, United States, 90048
      • Olga Voroshilovsky
    • Pasadena, California, United States, 91105
      • Institute for Regenerative Medicine and Clinical Research
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Boulder Medical Center
  • Connecticut
    • Avon, Connecticut, United States, 06001
      • Prime Healthcare - Anthony Roselli MD
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Washington Pain Center
  • Florida
    • Doral, Florida, United States, 33126
      • Continental Research Network
    • Miami, Florida, United States, 33144
      • Latin Foundation for Health
    • Stuart, Florida, United States, 34994
      • Primary Care Associates, P.A.
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Roman Medical Group
    • Hampton, Georgia, United States, 30228
      • Wellness Medicine
    • Macon, Georgia, United States, 31201
      • Ocmulgee Physicians
    • Macon, Georgia, United States, 31204
      • Macon Family Health Center Inc.
    • Rome, Georgia, United States, 30161
      • Your Personal Physician
    • Rome, Georgia, United States, 30165
      • Valley Health Care
    • Snellville, Georgia, United States, 30039
      • Dr. B. Abraham PC
    • Statesboro, Georgia, United States, 30458
      • Candler Internal Medicine
  • Illinois
    • Orland Park, Illinois, United States, 60467
      • Primary Health Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Women's Care Center
  • Michigan
    • Grandville, Michigan, United States, 49418
      • Healthy Heart Cardiology
    • Southfield, Michigan, United States, 48075
      • Heart Cardiology Consultants
  • New Jersey
    • Elizabeth, New Jersey, United States, 07208
      • Union Square Medical Associates, PC
    • Lyndhurst, New Jersey, United States, 07071
      • United Medical PC
  • New Mexico
    • Alamogordo, New Mexico, United States, 88310
      • Internal Medicine Specialists of Alamogordo, P.C.
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Rehabilitation Hospital
    • Albuquerque, New Mexico, United States, 87109
      • Sage Neuroscience Center
    • Albuquerque, New Mexico, United States, 87113
      • Geriatrics Associates, PAC
    • Las Cruces, New Mexico, United States, 88005
      • Isabel C Vigil MD
  • North Carolina
    • Charlotte, North Carolina, United States, 28210-0106
      • Larry F Berman MD PC
    • Durham, North Carolina, United States, 27704
      • Lakewood Pediatrics and Family Medicine
    • Gastonia, North Carolina, United States, 28054
      • Carolina Urology Partners
    • Greensboro, North Carolina, United States, 27401
      • Carolina Neurosurgery and Spine Associates
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Comprehensive Pain Center
    • Columbus, Ohio, United States, 43214
      • Knightsbridge Internal Medicine and Cardiology Associates, Inc
    • Columbus, Ohio, United States, 43215
      • Gateway Health and Wellness LLC
    • Mansfield, Ohio, United States, 44907
      • Robert E Barkett Jr MD
    • Marion, Ohio, United States, 43302
      • Midwestern Internal Medicine Associates (MIMA)
    • Reynoldsburg, Ohio, United States, 43068
      • Stonegate Family Health
    • Tallmadge, Ohio, United States, 44278
      • Primary Care Associates - Unity
  • Pennsylvania
    • Easton, Pennsylvania, United States, 18042
      • Easton Cardiovascular Associates
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Carolina Center for Advanced Management of Pain
    • Sumter, South Carolina, United States, 29150
      • Colonial Family Practice
    • Sumter, South Carolina, United States, 29150
      • Palmetto Adult Medicine
  • Tennessee
    • Oak Ridge, Tennessee, United States, 37830
      • Parkway Cardiology Associates
  • Texas
    • Fort Worth, Texas, United States, 76107
      • Mark A. Sanders, DO
  • Virginia
    • Emporia, Virginia, United States, 23847
      • Emporia Medical Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Male and female subjects over the age of 18, taking three or more medications, two of which are metabolized by the CYP450 pathway.

Description

Inclusion Criteria:

• Subject has care coordinated at the treating physician's outpatient clinic;
• Subject has provided written informed consent;
• Subject is taking at least three (3) regularly scheduled medications, excluding as needed (PRN) medications, over the counter medications and nutritional supplements; two (2) of which are known to be affected by genetic allelic variation.
• Subject's treating physician has a clinical suspicion that the subject is experiencing adverse signs or symptoms related to a prescribed medication or is not achieving the intended effect from the medication.

Exclusion Criteria:

• Subject has a history of chronic renal dysfunction, Chronic Kidney Disease Stage 4 or 5;
• Subject has a history of abnormal hepatic function within the last 2 years (INR >1.2 not attributable to anticoagulant medications, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) >1.5x normal, or suspected cirrhosis);
• Subject has a history of malabsorption (short gut syndrome);
• Subject has a history of any gastric or small bowel surgery;
• Subject is currently hospitalized;
• Subject is currently being treated with intravenous medication;
• Subject underwent prior pharmacogenomic testing with results reported within the last 12 months.

Subjects may be eligible within 60 days from the date of pharmacogenomic testing.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of meaningful change in drug regimen	The primary endpoint of the study is the binary occurrence of meaningful change in drug regimen, defined in each subject when: A genotype known to affect a drug the subject is taking is identified, and; The subject's treating physician makes at least one drug regimen change in concordance with the PharmD recommendations.	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the regimen of drugs controlled by genes of interest over the 12 months prior to enrollment and change in the regimen of drugs controlled by genes of interest over the 60 days following receipt of pharmacogenetic test results.		60 days
Number of ADR per month over the 12 months prior to enrollment and number of ADR per month over the 60 days following receipt of pharmacogenomic test results.		60 days
Frequency of genome-based PharmD recommendations to alter drug or dose.		60 days
Emergency department visits and hospitalizations	Emergency department visits over the 12 months prior to enrollment, emergency department visits over the 60 days following receipt of test results, hospitalizations over the 12 months prior to enrollment, and hospitalizations over the 60 days following receipt of test results.	60 days

Collaborators and Investigators

• Sponsor: Renaissance RX
• Collaborators: Syntactx

Publications and helpful links

General Publications

• Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011 Nov 24;365(21):2002-12. doi: 10.1056/NEJMsa1103053.
• Onder G, Petrovic M, Tangiisuran B, Meinardi MC, Markito-Notenboom WP, Somers A, Rajkumar C, Bernabei R, van der Cammen TJ. Development and validation of a score to assess risk of adverse drug reactions among in-hospital patients 65 years or older: the GerontoNet ADR risk score. Arch Intern Med. 2010 Jul 12;170(13):1142-8. doi: 10.1001/archinternmed.2010.153.
• Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998 Apr 15;279(15):1200-5. doi: 10.1001/jama.279.15.1200.
• Mallet L, Spinewine A, Huang A. The challenge of managing drug interactions in elderly people. Lancet. 2007 Jul 14;370(9582):185-191. doi: 10.1016/S0140-6736(07)61092-7.
• Epstein RS, Moyer TP, Aubert RE, O Kane DJ, Xia F, Verbrugge RR, Gage BF, Teagarden JR. Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study). J Am Coll Cardiol. 2010 Jun 22;55(25):2804-12. doi: 10.1016/j.jacc.2010.03.009. Epub 2010 Apr 8.
• Wang L, McLeod HL, Weinshilboum RM. Genomics and drug response. N Engl J Med. 2011 Mar 24;364(12):1144-53. doi: 10.1056/NEJMra1010600. No abstract available.
• Aronson JK. Adverse drug reactions--no farewell to harms. Br J Clin Pharmacol. 2007 Feb;63(2):131-5. doi: 10.1111/j.1365-2125.2006.02860.x. No abstract available.
• Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000 Oct 7;356(9237):1255-9. doi: 10.1016/S0140-6736(00)02799-9.
• Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, Milligan PE, Grice G, Lenzini P, Rettie AE, Aquilante CL, Grosso L, Marsh S, Langaee T, Farnett LE, Voora D, Veenstra DL, Glynn RJ, Barrett A, McLeod HL. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008 Sep;84(3):326-31. doi: 10.1038/clpt.2008.10. Epub 2008 Feb 27. Erratum In: Clin Pharmacol Ther. 2008 Sep;84(3):430.
• International Warfarin Pharmacogenetics Consortium, Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, Wagner MJ, Caldwell MD, Johnson JA. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009 Feb 19;360(8):753-64. doi: 10.1056/NEJMoa0809329. Erratum In: N Engl J Med. 2009 Oct 15;361(16):1613. Dosage error in article text.
• Garcia DA, Lopes RD, Hylek EM. New-onset atrial fibrillation and warfarin initiation: high risk periods and implications for new antithrombotic drugs. Thromb Haemost. 2010 Dec;104(6):1099-105. doi: 10.1160/TH10-07-0491. Epub 2010 Sep 30.
• Meckley LM, Gudgeon JM, Anderson JL, Williams MS, Veenstra DL. A policy model to evaluate the benefits, risks and costs of warfarin pharmacogenomic testing. Pharmacoeconomics. 2010;28(1):61-74. doi: 10.2165/11318240-000000000-00000.
• Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin Pharmacol Ther. 2011 Mar;89(3):464-7. doi: 10.1038/clpt.2010.279. Epub 2011 Jan 26.
• Gandhi TK, Weingart SN, Borus J, Seger AC, Peterson J, Burdick E, Seger DL, Shu K, Federico F, Leape LL, Bates DW. Adverse drug events in ambulatory care. N Engl J Med. 2003 Apr 17;348(16):1556-64. doi: 10.1056/NEJMsa020703.
• Huhtakangas J, Tetri S, Juvela S, Saloheimo P, Bode MK, Hillbom M. Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study. Stroke. 2011 Sep;42(9):2431-5. doi: 10.1161/STROKEAHA.111.615260. Epub 2011 Jul 28.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Anticipated): November 1, 2015

Study Registration Dates

• First Submitted: October 22, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimate): October 28, 2013

Study Record Updates

• Last Update Posted (Estimate): March 19, 2015
• Last Update Submitted That Met QC Criteria: March 18, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Emergency Department Visits; Pharmacogenomic; Hospitalizations; Adverse Drug Reactions
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: 2013-101