<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02191358</url>
  </required_header>
  <id_info>
    <org_study_id>Genelex 2014-01</org_study_id>
    <nct_id>NCT02191358</nct_id>
  </id_info>
  <brief_title>YouScript IMPACT Registry</brief_title>
  <acronym>IMPACT</acronym>
  <official_title>YouScript IMPACT (Improving Medication Protocols and Abating Cost of Treatment) Registry</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genelex Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Genelex Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This multicenter observational study aims to investigate the benefits of providing&#xD;
      pharmacogenetic testing with the YouScript Personalized Prescribing System which includes a&#xD;
      clinical decision support tool and individualized pharmacist recommendations to elderly&#xD;
      polypharmacy patients who are most at risk of adverse drug events. The YouScript system is&#xD;
      unique in identifying drug-gene, and drug-drug-gene interactions that are missed by existing&#xD;
      systems, and represent over 35% of significant interaction warnings. Data analysis will&#xD;
      assess the impact of recommendations for medication changes on clinical decision making,&#xD;
      patient outcomes, and healthcare resource utilization to determine which medications,&#xD;
      specialties, or patient segments derive the greatest benefit from this intervention. Data&#xD;
      gathered from patients enrolled in this study will be compared to patients matched on key&#xD;
      characteristics from Inovalon's MORE2 healthcare database.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND AND RATIONALE:&#xD;
&#xD;
      Genelex Corporation is a leader in comprehensive medication management based on the YouScript&#xD;
      clinical decision support tool and DNA drug sensitivity testing. Controlling prescription&#xD;
      drug adverse event risk is complex because more than 85% of patients have significant DNA&#xD;
      based variation in activity of the cytochrome p450 (CYP) enzymes that metabolize the majority&#xD;
      of the most commonly prescribed medicines. Polypharmacy, common in the elderly and&#xD;
      chronically ill further increases the risk of an adverse drug event (ADE). The public&#xD;
      healthcare problem resulting from these factors costs an estimated $289 billion per year in&#xD;
      excess health care costs.&#xD;
&#xD;
      The goal of the YouScript personalized prescribing system is to improve patient outcomes by&#xD;
      preventing ADEs caused by drug-drug, drug-gene and drug-drug-gene interactions. ADEs are&#xD;
      defined to include prescription and over-the-counter (OTC) drug overdose toxicity, adverse&#xD;
      drug reactions (ADRs), and treatment failures generally caused by properly prescribed&#xD;
      medications. The YouScript system prevents ADEs by the combined analysis of patient drug&#xD;
      regimens and individual genetics. YouScript DNA drug sensitivity testing includes five&#xD;
      enzymes in the cytochrome P450 (CYP) group (CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5).&#xD;
      YouScript synthesizes decades of publicly funded basic and clinical research to provide&#xD;
      actionable information to physicians treating patients.&#xD;
&#xD;
      Elderly patients are at greater risk of an ADE. Two-thirds of adults age 65 or older take one&#xD;
      or more prescription drugs daily. Patients age 60 years and older account for 10-17% of&#xD;
      hospitalizations and 51% of the deaths from ADEs, although this age group represents just 17%&#xD;
      of the U.S. population. Following discharge, 50% of patients with ADRs declined in one or&#xD;
      more activities of daily living, compared to 24% of patients without ADRs.&#xD;
&#xD;
      Although the value of pharmacogenetic testing and comprehensive gene-based medication&#xD;
      management is being recognized by clinicians, it is still not endorsed by many expert&#xD;
      committees and third party payers for most prescription drugs. The purpose of this study is&#xD;
      to meet the need for evidence that better demonstrates the impact of such comprehensive&#xD;
      gene-based medication management on healthcare resource utilization (HRU), clinical&#xD;
      decision-making, and patient outcomes. Therefore, the proposed study aims to assess the&#xD;
      impact of the YouScript Personal Prescribing System on HRU, clinical decision-making, and&#xD;
      clinical outcomes.&#xD;
&#xD;
      OBJECTIVES:&#xD;
&#xD;
      Primary objective:&#xD;
&#xD;
      To determine the impact of the YouScript Personalized Prescribing System on HRU.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
      To assess the impact of the YouScript Personalized Prescribing System on clinical&#xD;
      decision-making, including risk modification through dosage adjustment and medication change.&#xD;
&#xD;
      To assess the impact of the YouScript Personalized Prescribing System on the number of ADEs&#xD;
      experienced by patients.&#xD;
&#xD;
      STUDY DESIGN:&#xD;
&#xD;
      The study is designed as a prospective, non-interventional, observational study to assess the&#xD;
      real-world impact of the YouScript Personalized Prescribing System on HRU, provider clinical&#xD;
      decision-making, and ADEs. The decision to utilize the YouScript Personalized Prescribing&#xD;
      System and all treatment decisions will be made in accordance with usual care practice, and&#xD;
      will be made prior to the decision to participate in the study.&#xD;
&#xD;
      Outcomes will be compared between a group of prospectively enrolled patients undergoing&#xD;
      CYP2D6, CYP2C19, CYP2C9, VKORC1, CYP3A4, and CYP3A5 testing with the YouScript Personalized&#xD;
      Prescribing System at the discretion of their provider (i.e. &quot;tested&quot; patients) and data from&#xD;
      a group of similar patients included in Inovalon's MORE2 healthcare database meeting the same&#xD;
      enrollment criteria (excluding the YouScript testing) and matched on key characteristics to&#xD;
      the tested patients using propensity score matching. Sites will be queried regarding use of&#xD;
      other drug-drug interaction (DDI) systems to better distinguish the impact of YouScript vs.&#xD;
      other systems.&#xD;
&#xD;
      The study aims to initially enroll 1500 patients from 3-15 sites in the United States,&#xD;
      identified by Genelex. The study may be expanded up to 10,000 patients at additional sites in&#xD;
      the United States. The study duration is estimated to be at least 15 months, including 3&#xD;
      months for study set-up, 6 months or longer for patient enrollment depending on the rate of&#xD;
      accrual at each site, 4 months of per-patient follow-up and 2 months for study closeout.&#xD;
&#xD;
      A pilot study consisting of the first 150 patients enrolled will be conducted prior to&#xD;
      continuing enrollment in order to assist with planning the larger-scale study, such as&#xD;
      confirming appropriate length of follow-up necessary to observe patient outcomes, comparison&#xD;
      of patient baseline characteristics, identifying potential variables for propensity score&#xD;
      matching, sample size calculation, and necessary changes to case report forms.&#xD;
&#xD;
      After a discussion about the study with study staff and providing informed consent, baseline&#xD;
      data will be collected (described in more detail below), including a buccal swab or blood&#xD;
      sample, from patients undergoing YouScript testing. Follow-up data will be collected 120 days&#xD;
      after enrollment on all patients. Patients will be seen in the clinic or phoned (if a visit&#xD;
      is not scheduled in 120 days ± 14 days from baseline) and queried regarding HRU (including&#xD;
      number of hospitalizations, ER visits, provider office visits, and procedures), changes in&#xD;
      medications, reason for changes, and adverse drug events. This data will also be abstracted&#xD;
      from the medical record for completeness. In addition, providers utilizing YouScript will&#xD;
      also be surveyed regarding the usefulness of YouScript in their clinical decision-making.&#xD;
&#xD;
      Similar available data will be abstracted for a sample of presumably untested patients&#xD;
      included in the MORE2 registry database who meet eligibility criteria and are matched to&#xD;
      prospectively enrolled patients on key characteristics using propensity score matching.&#xD;
&#xD;
      CLINICAL ASSESSMENTS:&#xD;
&#xD;
      As this is an observational study, there are no mandatory visits. While the timing of actual&#xD;
      patient visits will occur at the discretion of the treating provider, it will be requested&#xD;
      that data be entered at baseline and again 120 days after enrollment regardless of the number&#xD;
      of times that a patient had been seen during that interval. All data will be collected and&#xD;
      entered by the sites directly into a web-based electronic data capture (EDC) system via&#xD;
      electronic case report forms (eCRFs).&#xD;
&#xD;
      After patients are screened and consented, the following variables will be collected at&#xD;
      baseline, with some being collected as part of the standard YouScript requisition form:&#xD;
      demographics, current smoking status, active medical conditions, liver or kidney dysfunction,&#xD;
      drugs of interest and other concomitant medications (including date of initiation of therapy,&#xD;
      dose, frequency, and indication, respectively), previous ADEs to any drug of interest, and&#xD;
      buccal swab/blood sample for YouScript testing. The site will not be required to enter data&#xD;
      collected on the YouScript requisition form into the eCRF.&#xD;
&#xD;
      The following follow-up data will be collected during a routinely scheduled visit, or by&#xD;
      phone if a visit is not scheduled, approximately 120 days after enrollment: number of&#xD;
      hospitalizations; ER visits, diagnostic or surgical procedures, and office visits since&#xD;
      baseline; Change/consider/monitor recommendations for drug regimen change(s) by the pharmacy&#xD;
      team; changes in drug regimen/dose for drugs of interest and concomitant medications since&#xD;
      baseline; reason for changing or not changing drug regimen/dose; ADEs since baseline; and&#xD;
      healthcare provider survey/questions regarding role and usefulness of YouScript in clinical&#xD;
      decision making. If a visit is not scheduled at 120 days ±14 days, the study staff will&#xD;
      contact patients by telephone and data will be collected. If patients choose to terminate&#xD;
      participation before completion of the 120-day follow---up, all follow-up data will be&#xD;
      collected, as well as the reason for discontinuation.&#xD;
&#xD;
      DATA ANALYSIS:&#xD;
&#xD;
      Complete analytical specifications, including tables and listings, will be fully detailed in&#xD;
      the statistical analysis plan (SAP). Descriptive analyses will be performed to gain an&#xD;
      understanding of the qualitative and quantitative nature of the data collected and the&#xD;
      characteristics of the sample studied. Summary statistics will be calculated and presented&#xD;
      for baseline characteristics and outcomes for tested and control groups separately.&#xD;
&#xD;
      Comparative analyses will be conducted to determine whether there are statistically&#xD;
      significant differences in specific quantitative outcomes between tested and control groups.&#xD;
      Because of propensity score matching between tested and control patients, unadjusted&#xD;
      comparative analysis will be performed and reported as the primary results. Adjusted analysis&#xD;
      using multiple regression models will be used to examine potential confounding effects that&#xD;
      cannot be addressed by the matching process. Exploratory analyses will be conducted to&#xD;
      explore the impact of YouScript in various subgroups and to identify potential subgroups&#xD;
      which will be most likely to benefit from YouScript, as deemed appropriate.&#xD;
&#xD;
      The first interim analysis will be conducted after data collection is complete for&#xD;
      approximately the first 150 prospectively enrolled patients (i.e. the pilot study) to&#xD;
      determine if any changes are necessary in the methods of the larger scale study. The second&#xD;
      interim analysis will be completed after data collection is complete for approximately 750&#xD;
      prospectively enrolled patients.&#xD;
&#xD;
      For the main analyses, differences in HRU at the 120-day follow-up will be determined by&#xD;
      comparing the mean number of hospitalizations, emergency room visits, diagnostic procedures,&#xD;
      surgical procedures, and clinic visits between the tested and untested groups. The impact of&#xD;
      YouScript on clinical decision making will be determined by comparing the mean number of&#xD;
      changes in drug regimen or dose between those who underwent YouScript testing and those that&#xD;
      did not. In addition, the number of ADEs experienced by patients during the 120-day study&#xD;
      will be compared between the tested and untested groups. Comparisons will be made with the&#xD;
      t-test (if the data are normally distributed), the Wilcoxon-Rank-Sum test (if the data are&#xD;
      continuous and not normally distributed), or the chi-squared (or Fisher exact) test if the&#xD;
      data are considered categorical. Multivariable linear regression models will be used to&#xD;
      examine the association of the YouScript Personalized Prescribing System with HRU, clinical&#xD;
      decision making, and ADEs, respectively, while controlling for potential confounding effects&#xD;
      from baseline characteristics not included in the propensity score matching process.&#xD;
&#xD;
      In tested patients only, HRU, number of ADEs, and number of changes in drug regimen/dose will&#xD;
      be examined in relationship to genotype, sample size permitting. Reasons for not changing&#xD;
      drug regimen or dose when a recommendation was made will be summarized qualitatively or be&#xD;
      analyzed quantitatively if possible. In addition, calculation of the drug-gene,&#xD;
      drug-drug-gene and drug-drug interaction recommendation acceptance rate (as defined by&#xD;
      whether a drug or dose was changed after a recommendation was made) will be calculated.&#xD;
      Provider feedback regarding whether the YouScript Personalized Prescribing System impacted&#xD;
      their clinical decisions will be summarized quantitatively and qualitatively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>4 Months</target_duration>
  <primary_outcome>
    <measure>Healthcare Resource Utilization</measure>
    <time_frame>120 days</time_frame>
    <description>The primary objective is to determine the impact of the YouScript Personalized Prescribing System on healthcare resource utilization. This will involve comparing the number of hospitalizations, number of ER visits, number of provider office visits, number of radiographic procedures, and number of surgeries for the tested group versus the untested group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical decision-making</measure>
    <time_frame>120 days</time_frame>
    <description>A secondary objective is to assess the impact of the YouScript Personalized Prescribing System on clinical decision-making, including risk modification through dosage adjustment. This will involve comparing changes in drug regimen/dose, as well as reasons for any changes and healthcare provider survey/question regarding the role and usefulness of YouScript in clinical decision making/or medication change for the tested group versus the untested group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Drug Events</measure>
    <time_frame>120 days</time_frame>
    <description>A secondary objective is to assess the impact of the YouScript Personalized Prescribing System on the number of adverse drug events experienced by patients. This will involve comparing the number of adverse events experienced by patients along with severity and relatedness for the tested group versus the untested group.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">800</enrollment>
  <condition>Adverse Drug Events</condition>
  <condition>Adverse Drug Reactions</condition>
  <condition>Drug Interaction Potentiation</condition>
  <condition>Drug Metabolism, Poor, CYP2D6-RELATED</condition>
  <condition>Drug Metabolism, Poor, CYP2C19-RELATED</condition>
  <condition>Cytochrome P450 Enzyme Deficiency</condition>
  <condition>Cytochrome P450 CYP2D6 Enzyme Deficiency</condition>
  <condition>Cytochrome P450 CYP2C9 Enzyme Deficiency</condition>
  <condition>Cytochrome P450 CYP2C19 Enzyme Deficiency</condition>
  <condition>Cytochrome P450 CYP3A Enzyme Deficiency</condition>
  <condition>Poor Metabolizer Due to Cytochrome P450 CYP2C9 Variant</condition>
  <condition>Poor Metabolizer Due to Cytochrome P450 CYP2C19 Variant</condition>
  <condition>Poor Metabolizer Due to Cytochrome P450 CYP2D6 Variant</condition>
  <arm_group>
    <arm_group_label>&quot;Tested&quot; patients (prospective)</arm_group_label>
    <description>Patients whose providers decide to have them undergo testing via the YouScript Personalized Prescribing System will be recruited for the study. Data will be gathered at baseline and 120 days later. The decision to utilize YouScript and all treatment decisions will be made at the discretion of the provider in accordance with their usual care practice, and will be made prior to the decision to participate in the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>&quot;Untested&quot; patients (retrospective)</arm_group_label>
    <description>Patients for comparison to the prospectively followed patients will be derived from Inovalon's MORE2 healthcare database. Patients meeting the same enrollment criteria (excluding the YouScript testing) will be matched on key characteristics to the tested patients. Outcomes will be compared between the prospectively enrolled patients undergoing pharmacogenetic testing with the YouScript Personalized Prescribing System at the discretion of their treating physician.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The study consists of patients age 65 and older who are currently on or initiating&#xD;
        treatment with at least one oral form of medication (excluding medications taken PRN) with&#xD;
        a significant drug-gene interaction as defined by black box warning, FDA cautionary&#xD;
        labeling, clinical literature or a YouScript algorithm-predicted significant effect. Those&#xD;
        meeting eligibility criteria and undergoing YouScript testing according to their provider's&#xD;
        usual care practice will be eligible for prospective enrollment into the &quot;tested&quot; group.&#xD;
        Those included in Inovalon's MORE2 healthcare database meeting enrollment criteria between&#xD;
        January 1, 2013 and June 30, 2013 will be eligible for inclusion in the &quot;untested&quot; group.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        INCLUSION CRITERIA: Prospectively enrolled study participants (i.e. &quot;tested&quot; patients) must&#xD;
        fulfill all of the following criteria to be eligible for enrollment into the study:&#xD;
&#xD;
          -  Age 65 or older&#xD;
&#xD;
          -  Willing and able to provide informed consent for study participation either directly&#xD;
             or by a legally authorized representative (LAR)&#xD;
&#xD;
          -  Undergoing testing through the YouScript Personalized Prescribing System as&#xD;
             recommended during the course of routine care, and ordering all of the following&#xD;
             tests: CYP2D6, CYP2C19, CYP2C9, VKORC1, CYP3A4, CYP3A5&#xD;
&#xD;
          -  Currently taking at least 3 prescription medications (any route of administration)&#xD;
&#xD;
          -  Initiated treatment with, or changed the dose of, at least 1 of the following oral&#xD;
             forms of medication (excluding medications taken PRN) within the previous 120 days&#xD;
             (generic name given with major U.S. brand name given in parentheses). These&#xD;
             medications are subject to significant drug---gene interactions as defined by FDA&#xD;
             boxed warning, FDA cautionary labeling, clinical literature or a YouScript&#xD;
             algorithm---predicted significant effect:&#xD;
&#xD;
        Amitriptyline (Elavil), Aripiprazole (Abilify), Atomoxetine (Strattera), Carvedilol&#xD;
        (Coreg), Celecoxib (Celebrex), Citalopram (Celexa), Clobazam (Onfi), Clomipramine&#xD;
        (Anafranil), Clopidogrel (Plavix), Clozapine (Clozaril), Codeine [Tylenol #3 (combo)],&#xD;
        Desipramine (Norpramin), Dextromethorphan (Delsym), Diazepam (Valium), Doxepin (Sinequan),&#xD;
        Escitalopram (Lexapro), Esomeprazole (Nexium), Fesoterodine (Toviaz), Flecainide&#xD;
        (Tambocor), Fluoxetine (Prozac), Flurbiprofen (Ansaid), Fluvoxamine (Luvox), Haloperidol&#xD;
        (Haldol), Hydrocodone (Zohydro), Ibuprofen (Motrin), Iloperidone (Fanapt), Imipramine&#xD;
        (Tofranil), Indomethacin (Indocin), Meloxicam (Mobic), Metoprolol (Toprol-XL), Mexiletine&#xD;
        (Mexitil), Nortriptyline (Pamelor), Omeprazole (Prilosec), Oxycodone (Oxycontin),&#xD;
        Paroxetine (Paxil), Perphenazine (Trilafon), Phenobarbital (Luminal), Phenytoin (Dilantin),&#xD;
        Pimozide (Orap), Piroxicam (Feldene), Proguanil [(Malarone (combo)], Propafenone (Rythmol),&#xD;
        Propranolol (Inderal), Risperidone (Risperdal), Sertraline (Zoloft), Tetrabenazine&#xD;
        (Xenazine), Thioridazine (Mellaril), Timolol (Apotimol), Tolterodine (Detrol), Torsemide&#xD;
        (Demadex), Tramadol (Ultram), Trimipramine (Surmontil), Venlafaxine (Effexor), Voriconazole&#xD;
        (Vfend), Vortioxetine (Brintellix)&#xD;
&#xD;
        For a list of the inclusion criteria adapted to the &quot;untested&quot; patients (retrospective&#xD;
        cohort), see the protocol.&#xD;
&#xD;
        EXCLUSION CRITERIA: Patients (prospective and retrospective) meeting any of the following&#xD;
        criteria will not be eligible for enrollment/inclusion in the study (ICD9 codes are&#xD;
        included for retrospective database patients):&#xD;
&#xD;
          -  Previous CYP testing (CPT codes 81225, 81226, 81227)&#xD;
&#xD;
          -  History of organ transplant (199.2; 238.77; 414.06; 414.07; 996.80---996.89; E878.0;&#xD;
             V42.0---V42.7; V42.81---V42.84; V42.89; V42.9; V45.87; V49.83; V58.44)&#xD;
&#xD;
          -  Patient currently receiving intravenous antibiotics&#xD;
&#xD;
          -  Currently taking immunosuppressants (azathioprine, cyclosporine, monoclonal&#xD;
             antibodies, corticosteroids)&#xD;
&#xD;
          -  Current malabsorption syndrome (579.0), including the following: Intestinal&#xD;
             malabsorption (579.8, 579.9), Postoperative malabsorption (579.3), Short bowel&#xD;
             syndrome (579.3)&#xD;
&#xD;
          -  Current hospitalization&#xD;
&#xD;
          -  Treatment of invasive solid tumors or hematologic malignancies in the last year,&#xD;
             excluding in situ cancers or non-melanoma skin cancer (basal cell carcinoma)&#xD;
&#xD;
          -  Currently malnourished, as determined by treating provider&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Diana Brixner, PhD, RPh</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dr. Michael Dao</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92844</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Colorado</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gill Heart Institute</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRC Clinics</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine &amp; Cardiology Associates</name>
      <address>
        <city>Fall River</city>
        <state>Massachusetts</state>
        <zip>02720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prima CARE</name>
      <address>
        <city>Fall River</city>
        <state>Massachusetts</state>
        <zip>02720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Clinic</name>
      <address>
        <city>Christiansburg</city>
        <state>Virginia</state>
        <zip>24073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.genomeweb.com/molecular-diagnostics/genelex-publishes-study-hoping-improve-pgx-panel-test-reimbursement-medicare</url>
    <description>Genelex Publishes Study Hoping to Improve PGx Panel Test Reimbursement; Medicare Remains Unconvinced</description>
  </link>
  <results_reference>
    <citation>Brixner D, Biltaji E, Bress A, Unni S, Ye X, Mamiya T, Ashcraft K, Biskupiak J. The effect of pharmacogenetic profiling with a clinical decision support tool on healthcare resource utilization and estimated costs in the elderly exposed to polypharmacy. J Med Econ. 2016;19(3):213-28. doi: 10.3111/13696998.2015.1110160. Epub 2015 Nov 11.</citation>
    <PMID>26478982</PMID>
  </results_reference>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <last_update_submitted>February 27, 2017</last_update_submitted>
  <last_update_submitted_qc>February 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cytochrome drug interactions</keyword>
  <keyword>Drug-drug interaction</keyword>
  <keyword>Drug-gene interaction</keyword>
  <keyword>Drug-drug-gene interaction</keyword>
  <keyword>Drug Metabolism</keyword>
  <keyword>Elderly</keyword>
  <keyword>Geriatric medicine</keyword>
  <keyword>Geriatrics</keyword>
  <keyword>Personalized medicine</keyword>
  <keyword>Pharmacist</keyword>
  <keyword>Pharmacogenetics</keyword>
  <keyword>Pharmacogenomics</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Polymorphism</keyword>
  <keyword>Polypharmacy</keyword>
  <keyword>Precision medicine</keyword>
  <keyword>Seniors</keyword>
  <keyword>YouScript</keyword>
  <keyword>CYP2C9</keyword>
  <keyword>CYP2C19</keyword>
  <keyword>CYP2D6</keyword>
  <keyword>CYP3A4</keyword>
  <keyword>CYP3A5</keyword>
  <keyword>VKORC1</keyword>
  <keyword>Amitriptyline</keyword>
  <keyword>Aripiprazole</keyword>
  <keyword>Atomoxetine</keyword>
  <keyword>Carvedilol</keyword>
  <keyword>Celecoxib</keyword>
  <keyword>Citalopram</keyword>
  <keyword>Clobazam</keyword>
  <keyword>Clomipramine</keyword>
  <keyword>Clopidogrel</keyword>
  <keyword>Clozapine</keyword>
  <keyword>Codeine</keyword>
  <keyword>Desipramine</keyword>
  <keyword>Dextromethorphan</keyword>
  <keyword>Diazepam</keyword>
  <keyword>Doxepin</keyword>
  <keyword>Escitalopram</keyword>
  <keyword>Esomeprazole</keyword>
  <keyword>Fesoterodine</keyword>
  <keyword>Flecainide</keyword>
  <keyword>Fluoxetine</keyword>
  <keyword>Flurbiprofen</keyword>
  <keyword>Fluvoxamine</keyword>
  <keyword>Haloperidol</keyword>
  <keyword>Hydrocodone</keyword>
  <keyword>Ibuprofen</keyword>
  <keyword>Iloperidone</keyword>
  <keyword>Imipramine</keyword>
  <keyword>Indomethacin</keyword>
  <keyword>Meloxicam</keyword>
  <keyword>Metoprolol</keyword>
  <keyword>Mexiletine</keyword>
  <keyword>Nortriptyline</keyword>
  <keyword>Omeprazole</keyword>
  <keyword>Oxycodone</keyword>
  <keyword>Paroxetine</keyword>
  <keyword>Perphenazine</keyword>
  <keyword>Phenobarbital</keyword>
  <keyword>Phenytoin</keyword>
  <keyword>Pimozide</keyword>
  <keyword>Piroxicam</keyword>
  <keyword>Proguanil</keyword>
  <keyword>Propafenone</keyword>
  <keyword>Propranolol</keyword>
  <keyword>Risperidone</keyword>
  <keyword>Sertraline</keyword>
  <keyword>Tetrabenazine</keyword>
  <keyword>Thioridazine</keyword>
  <keyword>Timolol</keyword>
  <keyword>Tolterodine</keyword>
  <keyword>Torsemide</keyword>
  <keyword>Tramadol</keyword>
  <keyword>Trimipramine</keyword>
  <keyword>Venlafaxine</keyword>
  <keyword>Voriconazole</keyword>
  <keyword>Vortioxetine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Drug-Related Side Effects and Adverse Reactions</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02191358
org study id: Genelex 2014-01
nct id: NCT02191358
lead sponsor: 
collaborator: 
has dmc: No
This multicenter observational study aims to investigate the benefits of providing
      pharmacogenetic testing with the YouScript Personalized Prescribing System which includes a
      clinical decision support tool and individualized pharmacist recommendations to elderly
      polypharmacy patients who are most at risk of adverse drug events. The YouScript system is
      unique in identifying drug-gene, and drug-drug-gene interactions that are missed by existing
      systems, and represent over 35% of significant interaction warnings. Data analysis will
      assess the impact of recommendations for medication changes on clinical decision making,
      patient outcomes, and healthcare resource utilization to determine which medications,
      specialties, or patient segments derive the greatest benefit from this intervention. Data
      gathered from patients enrolled in this study will be compared to patients matched on key
      characteristics from Inovalon's MORE2 healthcare database.
BACKGROUND AND RATIONALE:

      Genelex Corporation is a leader in comprehensive medication management based on the YouScript
      clinical decision support tool and DNA drug sensitivity testing. Controlling prescription
      drug adverse event risk is complex because more than 85% of patients have significant DNA
      based variation in activity of the cytochrome p450 (CYP) enzymes that metabolize the majority
      of the most commonly prescribed medicines. Polypharmacy, common in the elderly and
      chronically ill further increases the risk of an adverse drug event (ADE). The public
      healthcare problem resulting from these factors costs an estimated $289 billion per year in
      excess health care costs.

      The goal of the YouScript personalized prescribing system is to improve patient outcomes by
      preventing ADEs caused by drug-drug, drug-gene and drug-drug-gene interactions. ADEs are
      defined to include prescription and over-the-counter (OTC) drug overdose toxicity, adverse
      drug reactions (ADRs), and treatment failures generally caused by properly prescribed
      medications. The YouScript system prevents ADEs by the combined analysis of patient drug
      regimens and individual genetics. YouScript DNA drug sensitivity testing includes five
      enzymes in the cytochrome P450 (CYP) group (CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5).
      YouScript synthesizes decades of publicly funded basic and clinical research to provide
      actionable information to physicians treating patients.

      Elderly patients are at greater risk of an ADE. Two-thirds of adults age 65 or older take one
      or more prescription drugs daily. Patients age 60 years and older account for 10-17% of
      hospitalizations and 51% of the deaths from ADEs, although this age group represents just 17%
      of the U.S. population. Following discharge, 50% of patients with ADRs declined in one or
      more activities of daily living, compared to 24% of patients without ADRs.

      Although the value of pharmacogenetic testing and comprehensive gene-based medication
      management is being recognized by clinicians, it is still not endorsed by many expert
      committees and third party payers for most prescription drugs. The purpose of this study is
      to meet the need for evidence that better demonstrates the impact of such comprehensive
      gene-based medication management on healthcare resource utilization (HRU), clinical
      decision-making, and patient outcomes. Therefore, the proposed study aims to assess the
      impact of the YouScript Personal Prescribing System on HRU, clinical decision-making, and
      clinical outcomes.

      OBJECTIVES:

      Primary objective:

      To determine the impact of the YouScript Personalized Prescribing System on HRU.

      Secondary objectives:

      To assess the impact of the YouScript Personalized Prescribing System on clinical
      decision-making, including risk modification through dosage adjustment and medication change.

      To assess the impact of the YouScript Personalized Prescribing System on the number of ADEs
      experienced by patients.

      STUDY DESIGN:

      The study is designed as a prospective, non-interventional, observational study to assess the
      real-world impact of the YouScript Personalized Prescribing System on HRU, provider clinical
      decision-making, and ADEs. The decision to utilize the YouScript Personalized Prescribing
      System and all treatment decisions will be made in accordance with usual care practice, and
      will be made prior to the decision to participate in the study.

      Outcomes will be compared between a group of prospectively enrolled patients undergoing
      CYP2D6, CYP2C19, CYP2C9, VKORC1, CYP3A4, and CYP3A5 testing with the YouScript Personalized
      Prescribing System at the discretion of their provider (i.e. "tested" patients) and data from
      a group of similar patients included in Inovalon's MORE2 healthcare database meeting the same
      enrollment criteria (excluding the YouScript testing) and matched on key characteristics to
      the tested patients using propensity score matching. Sites will be queried regarding use of
      other drug-drug interaction (DDI) systems to better distinguish the impact of YouScript vs.
      other systems.

      The study aims to initially enroll 1500 patients from 3-15 sites in the United States,
      identified by Genelex. The study may be expanded up to 10,000 patients at additional sites in
      the United States. The study duration is estimated to be at least 15 months, including 3
      months for study set-up, 6 months or longer for patient enrollment depending on the rate of
      accrual at each site, 4 months of per-patient follow-up and 2 months for study closeout.

      A pilot study consisting of the first 150 patients enrolled will be conducted prior to
      continuing enrollment in order to assist with planning the larger-scale study, such as
      confirming appropriate length of follow-up necessary to observe patient outcomes, comparison
      of patient baseline characteristics, identifying potential variables for propensity score
      matching, sample size calculation, and necessary changes to case report forms.

      After a discussion about the study with study staff and providing informed consent, baseline
      data will be collected (described in more detail below), including a buccal swab or blood
      sample, from patients undergoing YouScript testing. Follow-up data will be collected 120 days
      after enrollment on all patients. Patients will be seen in the clinic or phoned (if a visit
      is not scheduled in 120 days ± 14 days from baseline) and queried regarding HRU (including
      number of hospitalizations, ER visits, provider office visits, and procedures), changes in
      medications, reason for changes, and adverse drug events. This data will also be abstracted
      from the medical record for completeness. In addition, providers utilizing YouScript will
      also be surveyed regarding the usefulness of YouScript in their clinical decision-making.

      Similar available data will be abstracted for a sample of presumably untested patients
      included in the MORE2 registry database who meet eligibility criteria and are matched to
      prospectively enrolled patients on key characteristics using propensity score matching.

      CLINICAL ASSESSMENTS:

      As this is an observational study, there are no mandatory visits. While the timing of actual
      patient visits will occur at the discretion of the treating provider, it will be requested
      that data be entered at baseline and again 120 days after enrollment regardless of the number
      of times that a patient had been seen during that interval. All data will be collected and
      entered by the sites directly into a web-based electronic data capture (EDC) system via
      electronic case report forms (eCRFs).

      After patients are screened and consented, the following variables will be collected at
      baseline, with some being collected as part of the standard YouScript requisition form:
      demographics, current smoking status, active medical conditions, liver or kidney dysfunction,
      drugs of interest and other concomitant medications (including date of initiation of therapy,
      dose, frequency, and indication, respectively), previous ADEs to any drug of interest, and
      buccal swab/blood sample for YouScript testing. The site will not be required to enter data
      collected on the YouScript requisition form into the eCRF.

      The following follow-up data will be collected during a routinely scheduled visit, or by
      phone if a visit is not scheduled, approximately 120 days after enrollment: number of
      hospitalizations; ER visits, diagnostic or surgical procedures, and office visits since
      baseline; Change/consider/monitor recommendations for drug regimen change(s) by the pharmacy
      team; changes in drug regimen/dose for drugs of interest and concomitant medications since
      baseline; reason for changing or not changing drug regimen/dose; ADEs since baseline; and
      healthcare provider survey/questions regarding role and usefulness of YouScript in clinical
      decision making. If a visit is not scheduled at 120 days ±14 days, the study staff will
      contact patients by telephone and data will be collected. If patients choose to terminate
      participation before completion of the 120-day follow---up, all follow-up data will be
      collected, as well as the reason for discontinuation.

      DATA ANALYSIS:

      Complete analytical specifications, including tables and listings, will be fully detailed in
      the statistical analysis plan (SAP). Descriptive analyses will be performed to gain an
      understanding of the qualitative and quantitative nature of the data collected and the
      characteristics of the sample studied. Summary statistics will be calculated and presented
      for baseline characteristics and outcomes for tested and control groups separately.

      Comparative analyses will be conducted to determine whether there are statistically
      significant differences in specific quantitative outcomes between tested and control groups.
      Because of propensity score matching between tested and control patients, unadjusted
      comparative analysis will be performed and reported as the primary results. Adjusted analysis
      using multiple regression models will be used to examine potential confounding effects that
      cannot be addressed by the matching process. Exploratory analyses will be conducted to
      explore the impact of YouScript in various subgroups and to identify potential subgroups
      which will be most likely to benefit from YouScript, as deemed appropriate.

      The first interim analysis will be conducted after data collection is complete for
      approximately the first 150 prospectively enrolled patients (i.e. the pilot study) to
      determine if any changes are necessary in the methods of the larger scale study. The second
      interim analysis will be completed after data collection is complete for approximately 750
      prospectively enrolled patients.

      For the main analyses, differences in HRU at the 120-day follow-up will be determined by
      comparing the mean number of hospitalizations, emergency room visits, diagnostic procedures,
      surgical procedures, and clinic visits between the tested and untested groups. The impact of
      YouScript on clinical decision making will be determined by comparing the mean number of
      changes in drug regimen or dose between those who underwent YouScript testing and those that
      did not. In addition, the number of ADEs experienced by patients during the 120-day study
      will be compared between the tested and untested groups. Comparisons will be made with the
      t-test (if the data are normally distributed), the Wilcoxon-Rank-Sum test (if the data are
      continuous and not normally distributed), or the chi-squared (or Fisher exact) test if the
      data are considered categorical. Multivariable linear regression models will be used to
      examine the association of the YouScript Personalized Prescribing System with HRU, clinical
      decision making, and ADEs, respectively, while controlling for potential confounding effects
      from baseline characteristics not included in the propensity score matching process.

      In tested patients only, HRU, number of ADEs, and number of changes in drug regimen/dose will
      be examined in relationship to genotype, sample size permitting. Reasons for not changing
      drug regimen or dose when a recommendation was made will be summarized qualitatively or be
      analyzed quantitatively if possible. In addition, calculation of the drug-gene,
      drug-drug-gene and drug-drug interaction recommendation acceptance rate (as defined by
      whether a drug or dose was changed after a recommendation was made) will be calculated.
      Provider feedback regarding whether the YouScript Personalized Prescribing System impacted
      their clinical decisions will be summarized quantitatively and qualitatively.
observational model: Other
time perspective: Prospective
measure: Healthcare Resource Utilization
time frame: 120 days
description: The primary objective is to determine the impact of the YouScript Personalized Prescribing System on healthcare resource utilization. This will involve comparing the number of hospitalizations, number of ER visits, number of provider office visits, number of radiographic procedures, and number of surgeries for the tested group versus the untested group.
measure: Clinical decision-making
time frame: 120 days
description: A secondary objective is to assess the impact of the YouScript Personalized Prescribing System on clinical decision-making, including risk modification through dosage adjustment. This will involve comparing changes in drug regimen/dose, as well as reasons for any changes and healthcare provider survey/question regarding the role and usefulness of YouScript in clinical decision making/or medication change for the tested group versus the untested group.
measure: Adverse Drug Events
time frame: 120 days
description: A secondary objective is to assess the impact of the YouScript Personalized Prescribing System on the number of adverse drug events experienced by patients. This will involve comparing the number of adverse events experienced by patients along with severity and relatedness for the tested group versus the untested group.
arm group label: "Tested" patients (prospective)
description: Patients whose providers decide to have them undergo testing via the YouScript Personalized Prescribing System will be recruited for the study. Data will be gathered at baseline and 120 days later. The decision to utilize YouScript and all treatment decisions will be made at the discretion of the provider in accordance with their usual care practice, and will be made prior to the decision to participate in the study.
arm group label: "Untested" patients (retrospective)
description: Patients for comparison to the prospectively followed patients will be derived from Inovalon's MORE2 healthcare database. Patients meeting the same enrollment criteria (excluding the YouScript testing) will be matched on key characteristics to the tested patients. Outcomes will be compared between the prospectively enrolled patients undergoing pharmacogenetic testing with the YouScript Personalized Prescribing System at the discretion of their treating physician.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Diana Brixner, PhD, RPh
role: Principal Investigator
affiliation: University of Utah
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://www.genomeweb.com/molecular-diagnostics/genelex-publishes-study-hoping-improve-pgx-panel-test-reimbursement-medicare
description: Genelex Publishes Study Hoping to Improve PGx Panel Test Reimbursement; Medicare Remains Unconvinced
citation: Brixner D, Biltaji E, Bress A, Unni S, Ye X, Mamiya T, Ashcraft K, Biskupiak J. The effect of pharmacogenetic profiling with a clinical decision support tool on healthcare resource utilization and estimated costs in the elderly exposed to polypharmacy. J Med Econ. 2016;19(3):213-28. doi: 10.3111/13696998.2015.1110160. Epub 2015 Nov 11.
PMID: 26478982
responsible party type: Sponsor
mesh term: Drug-Related Side Effects and Adverse Reactions