<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/NCT03276637</url>
  </required_header>
  <id_info>
    <org_study_id>The MilSeq Project</org_study_id>
    <nct_id>NCT03276637</nct_id>
  </id_info>
  <brief_title>Enabling Personalized Medicine Through Exome Sequencing in the U.S. Air Force</brief_title>
  <acronym>MilSeq</acronym>
  <official_title>The MilSeq Project: Enabling Personalized Medicine Through Exome Sequencing in the U.S. Air Force</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The MilSeq Project is a nonrandomized, prospective pilot study of whole exome sequencing&#xD;
      (WES) in the U.S. Air Force. The purpose of this study is to explore the implementation of&#xD;
      WES into clinical medical care in the military health system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this effort is to investigate: (a) military healthcare providers' (HCPs')&#xD;
      genomic knowledge before and after receiving a genomic educational primer and after&#xD;
      disclosing whole exome sequencing (WES) results to begin to assess the genomic educational&#xD;
      needs of military HCPs; (b) active-duty Airmen's knowledge and perceptions of genomic&#xD;
      sequencing (GS); (c) reasons why active-duty Airmen choose to participate, or not to&#xD;
      participate, in research involving GS; (d) how WES study participants, including HCPs and&#xD;
      sequenced active-duty Airmen (patient-participants), respond to and use WES results; (e) the&#xD;
      collection of medical, behavioral, and healthcare utilization outcomes related to the&#xD;
      clinical integration of WES in the military; (f) how return of WES results and integration&#xD;
      into the Electronic Medical Record (EMR) do or do not impact perceptions of mission readiness&#xD;
      and duty assignments. Given the lack of prior research in this area in the Air Force and the&#xD;
      broad number of topics of interest, the aims of the study are predominantly exploratory and&#xD;
      results may be hypothesis generating.&#xD;
&#xD;
      The MilSeq Project will be conducted in two sequential phases. Phase I of the study will&#xD;
      recruit, consent, and enroll approximately 75 ostensibly healthy active-duty Airmen who&#xD;
      receive medical care in military Primary Care, Internal Medicine, and/or Family Practice&#xD;
      settings to take a baseline survey. This survey will be administered to explore active-duty&#xD;
      Airmen's perceptions of and preferences for GS, identify motivations and barriers to&#xD;
      active-duty Airmen participating in a WES study, and assess interest in taking part in the&#xD;
      WES study.&#xD;
&#xD;
      Phase II of the study will recruit, consent, and enroll 75 ostensibly healthy active-duty&#xD;
      Airmen who receive medical care in military Primary Care, Internal Medicine and/or Family&#xD;
      Practice settings who in their baseline survey expressed interest in receiving WES through a&#xD;
      research study. WES will be performed on each enrolled patient-participant. The result will&#xD;
      be disclosed by an HCP-participant and permanently integrated into the patient-participant's&#xD;
      EMR. Phase II will also recruit 10-20 military Primary Care, Internal Medicine, and/or Family&#xD;
      Practice HCPs and consent them to participate in the study. The HCPs will receive an&#xD;
      educational primer in genomics and will disclose WES results to Airmen participants.&#xD;
&#xD;
      There are a number of potential benefits and challenges to incorporating genomic medicine&#xD;
      into the military, some that are relevant to the broader civilian community, but some that&#xD;
      are unique to this population. Some of these challenges include: (a) how GS may or may not&#xD;
      affect the perception of fitness for duty; (b) how genomic discrimination may or may not&#xD;
      occur in the military setting; (c) how to best deal with unanticipated findings; and (d) how&#xD;
      genomic results can be practically integrated into a military setting. In this pilot study,&#xD;
      these potential opportunities and challenges will be explored, which will provide a basis for&#xD;
      future study and begin to inform decisions regarding clinical care of active-duty service&#xD;
      members.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 23, 2017</start_date>
  <completion_date type="Actual">January 11, 2020</completion_date>
  <primary_completion_date type="Actual">June 22, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions</measure>
    <time_frame>Baseline and 6 weeks post disclosure of genomic sequencing results (approx. 43 weeks after baseline)</time_frame>
    <description>Assessed using a novel measure of perceptions about use of genetic information for military career duty assignment decisions on a 1-5 scale, where higher scores indicate more positive attitudes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Genomic Sequencing Findings</measure>
    <time_frame>Results disclosure (within 1 month of sequencing completion)</time_frame>
    <description>Analysis of whole exome sequencing results identified the number of participants with genomic findings, including monogenic disease risk, carrier status, and risk allele presence.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Active-duty Airmen Reported Health Care Utilization Related to Study Results</measure>
    <time_frame>6 weeks post-disclosure (approx. 43 weeks after baseline)</time_frame>
    <description>Participants' health care utilization was assessed through a combination of medical record reviews and novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS). Survey self-report data were compared to services and procedures indicated on medical record review.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing</measure>
    <time_frame>Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)</time_frame>
    <description>Adapted measures assessed participants' attitudes toward genetic information, trust of physicians and the military regarding use of genetic information. (Hall et al. 2006). Scores are summed, with higher scores on a 4-20 scale representing greater trust.&#xD;
A novel survey item at baseline and 6-weeks post-disclosure asked participants to rate the usefulness of whole genome sequencing results for managing health now on a 1-10 scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Active-duty Airmen's Health Perceptions</measure>
    <time_frame>Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)</time_frame>
    <description>Assessed using a validated measure of subjective perceptions about health status. (Latham 2013, DeSalvo 2006). Responses are on a 1 - 5 scale, where higher scores indicate more positive responses.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">93</enrollment>
  <condition>Healthy Adults</condition>
  <condition>Genetic Predisposition to Disease</condition>
  <arm_group>
    <arm_group_label>Healthy Active-Duty Airmen Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Whole exome sequencing</intervention_name>
    <description>Whole exome sequencing at 125x coverage (i.e., at least 125 sequencing reads covering each position within the exome region of interest) performed at the Laboratory of Molecular Medicine's Clinical Laboratory Improvement Amendments (CLIA) certified laboratory on 75 enrolled individuals</description>
    <arm_group_label>Healthy Active-Duty Airmen Cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Patient-Participant Inclusion Criteria:&#xD;
&#xD;
          -  18 years or older&#xD;
&#xD;
          -  An active Air Force Airman&#xD;
&#xD;
          -  Fluent in English&#xD;
&#xD;
          -  Seen or eligible to be seen by a provider at Wilford Hall Ambulatory Surgical Center&#xD;
             at Joint Base San Antonio (JBSA) Lackland Air Force Base&#xD;
&#xD;
        Healthcare Provider-Participant Inclusion Criterion&#xD;
&#xD;
          -  An active or Department of Defense civilian Primary Care, Internal Medicine, or Family&#xD;
             Practice Healthcare Provider (Physician, Physician Assistant, or Nurse Practitioner)&#xD;
             or resident practicing at Wilford Hall Ambulatory Surgical Center at JBSA Lackland Air&#xD;
             Force Base&#xD;
&#xD;
        Patient-Participant Exclusion Criteria:&#xD;
&#xD;
          -  Those who do not meet the above inclusion criteria&#xD;
&#xD;
          -  Those with clinically concerning scores on anxiety and distress scales in baseline&#xD;
             survey&#xD;
&#xD;
          -  Trainees (basic military training or tech school)&#xD;
&#xD;
          -  Airmen with an active change of duty station order or deployment order and expected to&#xD;
             leave San Antonio in 6 months or less&#xD;
&#xD;
          -  Airmen expected to be discharged from the Air Force in 6 months or less&#xD;
&#xD;
        Healthcare Provider-Participant Exclusion Criteria:&#xD;
&#xD;
          -  Providers who do not meet the above inclusion criteria&#xD;
&#xD;
          -  Providers with an active change of duty station order or deployment order and expected&#xD;
             to leave San Antonio in 6 months or less&#xD;
&#xD;
          -  Providers expected to be discharged from the Air Force in 6 months or less&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Joint Base San Antonio Lackland Air Force Base - 59th Medical Wing</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>McMorrow D. The $100 genome: implications for the DoD. Technical Report. McLean, Virginia: The MITRE Corporation; 2010.</citation>
  </reference>
  <reference>
    <citation>De Castro M, Biesecker LG, Turner C, Brenner R, Witkop C, Mehlman M, Bradburne C, Green RC. Genomic medicine in the military. NPJ Genom Med. 2016 Jan 13;1:15008. doi: 10.1038/npjgenmed.2015.8. eCollection 2016.</citation>
    <PMID>29263806</PMID>
  </reference>
  <reference>
    <citation>Collins FS, Guttmacher AE. Genetics moves into the medical mainstream. JAMA. 2001 Nov 14;286(18):2322-4. doi: 10.1001/jama.286.18.2322. No abstract available.</citation>
    <PMID>11710899</PMID>
  </reference>
  <reference>
    <citation>Collins FS, Green ED, Guttmacher AE, Guyer MS; US National Human Genome Research Institute. A vision for the future of genomics research. Nature. 2003 Apr 24;422(6934):835-47. doi: 10.1038/nature01626. Epub 2003 Apr 14. No abstract available.</citation>
    <PMID>12695777</PMID>
  </reference>
  <reference>
    <citation>McCarthy JJ, McLeod HL, Ginsburg GS. Genomic medicine: a decade of successes, challenges, and opportunities. Sci Transl Med. 2013 Jun 12;5(189):189sr4. doi: 10.1126/scitranslmed.3005785.</citation>
    <PMID>23761042</PMID>
  </reference>
  <reference>
    <citation>Green RC, Rehm HL, Kohane IS. Clinical genome sequencing. In: Ginsburg GS, Willard HF, eds. Genomic and Personalized Medicine. 2nd ed. San Diego: Academic Press; 2013:102-22.</citation>
  </reference>
  <reference>
    <citation>Christensen KD, Vassy JL, Jamal L, Lehmann LS, Slashinski MJ, Perry DL, Robinson JO, Blumenthal-Barby J, Feuerman LZ, Murray MF, Green RC, McGuire AL; MedSeq Project Team. Are physicians prepared for whole genome sequencing? a qualitative analysis. Clin Genet. 2016 Feb;89(2):228-34. doi: 10.1111/cge.12626. Epub 2015 Jul 7.</citation>
    <PMID>26080898</PMID>
  </reference>
  <reference>
    <citation>Vassy JL, Christensen KD, Slashinski MJ, Lautenbach DM, Raghavan S, Robinson JO, Blumenthal-Barby J, Feuerman LZ, Lehmann LS, Murray MF, Green RC, McGuire AL. 'Someday it will be the norm': physician perspectives on the utility of genome sequencing for patient care in the MedSeq Project. Per Med. 2015;12(1):23-32. doi: 10.2217/pme.14.68.</citation>
    <PMID>25642274</PMID>
  </reference>
  <reference>
    <citation>Vassy JL, Lautenbach DM, McLaughlin HM, Kong SW, Christensen KD, Krier J, Kohane IS, Feuerman LZ, Blumenthal-Barby J, Roberts JS, Lehmann LS, Ho CY, Ubel PA, MacRae CA, Seidman CE, Murray MF, McGuire AL, Rehm HL, Green RC; MedSeq Project. The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine. Trials. 2014 Mar 20;15:85. doi: 10.1186/1745-6215-15-85.</citation>
    <PMID>24645908</PMID>
  </reference>
  <reference>
    <citation>Johnston JJ, Lewis KL, Ng D, Singh LN, Wynter J, Brewer C, Brooks BP, Brownell I, Candotti F, Gonsalves SG, Hart SP, Kong HH, Rother KI, Sokolic R, Solomon BD, Zein WM, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG. Individualized iterative phenotyping for genome-wide analysis of loss-of-function mutations. Am J Hum Genet. 2015 Jun 4;96(6):913-25. doi: 10.1016/j.ajhg.2015.04.013.</citation>
    <PMID>26046366</PMID>
  </reference>
  <reference>
    <citation>Green RC, Lautenbach D, McGuire AL. GINA, genetic discrimination, and genomic medicine. N Engl J Med. 2015 Jan 29;372(5):397-9. doi: 10.1056/NEJMp1404776. No abstract available.</citation>
    <PMID>25629736</PMID>
  </reference>
  <reference>
    <citation>Robinson JO, Carroll TM, Feuerman LZ, Perry DL, Hoffman-Andrews L, Walsh RC, Christensen KD, Green RC, McGuire AL; MedSeq Project Team. Participants and Study Decliners' Perspectives About the Risks of Participating in a Clinical Trial of Whole Genome Sequencing. J Empir Res Hum Res Ethics. 2016 Feb;11(1):21-30. doi: 10.1177/1556264615624078. Epub 2016 Feb 28.</citation>
    <PMID>26928896</PMID>
  </reference>
  <reference>
    <citation>Vassy JL, McLaughlin HM, MacRae CA, Seidman CE, Lautenbach D, Krier JB, Lane WJ, Kohane IS, Murray MF, McGuire AL, Rehm HL, Green RC. A one-page summary report of genome sequencing for the healthy adult. Public Health Genomics. 2015;18(2):123-9. doi: 10.1159/000370102. Epub 2015 Jan 21. Erratum In: Public Health Genomics. 2015 Apr;18(3):191. McLaughlin, Heather L [corrected to McLaughlin, Heather M].</citation>
    <PMID>25612602</PMID>
  </reference>
  <reference>
    <citation>Krier J, McLaughlin HM, Lane WJ, et al. The return of pharmacogenomic variants in the MedSeq Project: reporting approach and physician response. Annual Meeting of the American Society of Human Genetics. Boston, MA2013</citation>
  </reference>
  <reference>
    <citation>Lane WJ, Westhoff CM, Uy JM, Aguad M, Smeland-Wagman R, Kaufman RM, Rehm HL, Green RC, Silberstein LE; MedSeq Project. Comprehensive red blood cell and platelet antigen prediction from whole genome sequencing: proof of principle. Transfusion. 2016 Mar;56(3):743-54. doi: 10.1111/trf.13416. Epub 2015 Dec 3.</citation>
    <PMID>26634332</PMID>
  </reference>
  <reference>
    <citation>Giovanni MA, Krier J, Vassy JL, Lautenbach DM, Green RC, Murray MF. A brief curriculum for physician orientation to clinical whole genome sequencing. American Society of Human Genetics Annual Meeting. Boston, MA2013.</citation>
  </reference>
  <reference>
    <citation>Krier JB, Blout CB, D L, et al. Communication and management of genomic sequencing results by non-geneticist physicians. American Society of Human Genetics; 2015; Baltimore, MD.</citation>
  </reference>
  <reference>
    <citation>Green RC, Goddard KAB, Jarvik GP, Amendola LM, Appelbaum PS, Berg JS, Bernhardt BA, Biesecker LG, Biswas S, Blout CL, Bowling KM, Brothers KB, Burke W, Caga-Anan CF, Chinnaiyan AM, Chung WK, Clayton EW, Cooper GM, East K, Evans JP, Fullerton SM, Garraway LA, Garrett JR, Gray SW, Henderson GE, Hindorff LA, Holm IA, Lewis MH, Hutter CM, Janne PA, Joffe S, Kaufman D, Knoppers BM, Koenig BA, Krantz ID, Manolio TA, McCullough L, McEwen J, McGuire A, Muzny D, Myers RM, Nickerson DA, Ou J, Parsons DW, Petersen GM, Plon SE, Rehm HL, Roberts JS, Robinson D, Salama JS, Scollon S, Sharp RR, Shirts B, Spinner NB, Tabor HK, Tarczy-Hornoch P, Veenstra DL, Wagle N, Weck K, Wilfond BS, Wilhelmsen K, Wolf SM, Wynn J, Yu JH; CSER Consortium. Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine. Am J Hum Genet. 2016 Jun 2;98(6):1051-1066. doi: 10.1016/j.ajhg.2016.04.011. Epub 2016 May 12. Erratum In: Am J Hum Genet. 2016 Jul 7;99(1):246.</citation>
    <PMID>27181682</PMID>
  </reference>
  <reference>
    <citation>Berg JS, Agrawal PB, Bailey DB Jr, Beggs AH, Brenner SE, Brower AM, Cakici JA, Ceyhan-Birsoy O, Chan K, Chen F, Currier RJ, Dukhovny D, Green RC, Harris-Wai J, Holm IA, Iglesias B, Joseph G, Kingsmore SF, Koenig BA, Kwok PY, Lantos J, Leeder SJ, Lewis MA, McGuire AL, Milko LV, Mooney SD, Parad RB, Pereira S, Petrikin J, Powell BC, Powell CM, Puck JM, Rehm HL, Risch N, Roche M, Shieh JT, Veeraraghavan N, Watson MS, Willig L, Yu TW, Urv T, Wise AL. Newborn Sequencing in Genomic Medicine and Public Health. Pediatrics. 2017 Feb;139(2):e20162252. doi: 10.1542/peds.2016-2252. Epub 2017 Jan 17.</citation>
    <PMID>28096516</PMID>
  </reference>
  <reference>
    <citation>Kaphingst KA, Facio FM, Cheng MR, Brooks S, Eidem H, Linn A, Biesecker BB, Biesecker LG. Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet. 2012 Nov;82(5):408-15. doi: 10.1111/j.1399-0004.2012.01909.x. Epub 2012 Aug 7.</citation>
    <PMID>22694298</PMID>
  </reference>
  <reference>
    <citation>Bowling BV, Acra EE, Wang L, Myers MF, Dean GE, Markle GC, Moskalik CL, Huether CA. Development and evaluation of a genetics literacy assessment instrument for undergraduates. Genetics. 2008 Jan;178(1):15-22. doi: 10.1534/genetics.107.079533.</citation>
    <PMID>18202354</PMID>
  </reference>
  <reference>
    <citation>Gray SW, Hicks-Courant K, Cronin A, Rollins BJ, Weeks JC. Physicians' attitudes about multiplex tumor genomic testing. J Clin Oncol. 2014 May 1;32(13):1317-23. doi: 10.1200/JCO.2013.52.4298. Epub 2014 Mar 24.</citation>
    <PMID>24663044</PMID>
  </reference>
  <reference>
    <citation>Selim AJ, Rogers W, Qian SX, Brazier J, Kazis LE. A preference-based measure of health: the VR-6D derived from the veterans RAND 12-Item Health Survey. Qual Life Res. 2011 Oct;20(8):1337-47. doi: 10.1007/s11136-011-9866-y. Epub 2011 Feb 19.</citation>
    <PMID>21336657</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <results_first_submitted>January 31, 2021</results_first_submitted>
  <results_first_submitted_qc>April 13, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 6, 2021</results_first_posted>
  <last_update_submitted>April 13, 2021</last_update_submitted>
  <last_update_submitted_qc>April 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Robert C. Green, MD, MPH</investigator_full_name>
    <investigator_title>Professor of Medicine, Division of Genetics, Department of Medicine</investigator_title>
  </responsible_party>
  <keyword>Whole Genome Sequencing</keyword>
  <keyword>Whole Exome Sequencing</keyword>
  <keyword>Military</keyword>
  <keyword>Air Force</keyword>
  <keyword>Disease Susceptibility</keyword>
  <keyword>Genetic Predisposition to Disease</keyword>
  <keyword>Disease Attributes</keyword>
  <keyword>Pathologic Processes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Disease Susceptibility</mesh_term>
    <mesh_term>Genetic Predisposition to Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 30, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT03276637/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Healthy Active-Duty Airmen Cohort</title>
          <description>Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.&#xD;
Whole exome sequencing: Whole exome sequencing at 125x coverage (i.e., at least 125 sequencing reads covering each position within the exome region of interest) performed at the Laboratory of Molecular Medicine's Clinical Laboratory Improvement Amendments (CLIA) certified laboratory on 75 enrolled individuals</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="93"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Pre Survey</title>
              <participants_list>
                <participants group_id="P1" count="93"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Underwent Sequencing</title>
              <participants_list>
                <participants group_id="P1" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Post Survey</title>
              <participants_list>
                <participants group_id="P1" count="69"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="69"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Healthy Active-Duty Airmen Cohort</title>
          <description>Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.&#xD;
Whole exome sequencing: Whole exome sequencing at 125x coverage (i.e., at least 125 sequencing reads covering each position within the exome region of interest) performed at the Laboratory of Molecular Medicine's CLIA certified laboratory on 75 enrolled individuals</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="93"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="93"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.75" spread="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race/Ethnicity</title>
              <category_list>
                <category>
                  <title>Hispanic or Lation</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-Hispanic White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-Hispanic Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Prefer Not to Answer</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions</title>
        <description>Assessed using a novel measure of perceptions about use of genetic information for military career duty assignment decisions on a 1-5 scale, where higher scores indicate more positive attitudes.</description>
        <time_frame>Baseline and 6 weeks post disclosure of genomic sequencing results (approx. 43 weeks after baseline)</time_frame>
        <population>69 participants completed follow-up survey</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Active-Duty Airmen Cohort</title>
            <description>Ostensibly healthy, active-duty Airmen who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving exome sequencing (ES) undergo ES and have the results returned to them.</description>
          </group>
        </group_list>
        <measure>
          <title>Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions</title>
          <description>Assessed using a novel measure of perceptions about use of genetic information for military career duty assignment decisions on a 1-5 scale, where higher scores indicate more positive attitudes.</description>
          <population>69 participants completed follow-up survey</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.62" spread="0.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6-weeks post-disclosure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.66" spread="0.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Genomic Sequencing Findings</title>
        <description>Analysis of whole exome sequencing results identified the number of participants with genomic findings, including monogenic disease risk, carrier status, and risk allele presence.</description>
        <time_frame>Results disclosure (within 1 month of sequencing completion)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Active-Duty Airmen Cohort</title>
            <description>Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.&#xD;
Whole exome sequencing: Whole exome sequencing at 125x coverage (i.e., at least 125 sequencing reads covering each position within the exome region of interest) performed at the Laboratory of Molecular Medicine's CLIA certified laboratory on 75 enrolled individuals</description>
          </group>
        </group_list>
        <measure>
          <title>Genomic Sequencing Findings</title>
          <description>Analysis of whole exome sequencing results identified the number of participants with genomic findings, including monogenic disease risk, carrier status, and risk allele presence.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Monogenic disease findings</title>
              <category_list>
                <category>
                  <title>Present</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Present</title>
                  <measurement_list>
                    <measurement group_id="O1" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Carrier status findings</title>
              <category_list>
                <category>
                  <title>Present</title>
                  <measurement_list>
                    <measurement group_id="O1" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Present</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Risk Allele findings</title>
              <category_list>
                <category>
                  <title>Present</title>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Present</title>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Active-duty Airmen Reported Health Care Utilization Related to Study Results</title>
        <description>Participants' health care utilization was assessed through a combination of medical record reviews and novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS). Survey self-report data were compared to services and procedures indicated on medical record review.</description>
        <time_frame>6 weeks post-disclosure (approx. 43 weeks after baseline)</time_frame>
        <population>69 participants completed follow-up survey and several participants selected more than one answer for 83 total responses.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Active-Duty Airmen Cohort</title>
            <description>Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.&#xD;
Whole exome sequencing: Whole exome sequencing at 125x coverage (i.e., at least 125 sequencing reads covering each position within the exome region of interest) performed at the Laboratory of Molecular Medicine's CLIA certified laboratory on 75 enrolled individuals</description>
          </group>
        </group_list>
        <measure>
          <title>Active-duty Airmen Reported Health Care Utilization Related to Study Results</title>
          <description>Participants' health care utilization was assessed through a combination of medical record reviews and novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS). Survey self-report data were compared to services and procedures indicated on medical record review.</description>
          <population>69 participants completed follow-up survey and several participants selected more than one answer for 83 total responses.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="83"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change in diet</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in exercise</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in use of vitamin supplements</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in use of medication</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing</title>
        <description>Adapted measures assessed participants' attitudes toward genetic information, trust of physicians and the military regarding use of genetic information. (Hall et al. 2006). Scores are summed, with higher scores on a 4-20 scale representing greater trust.&#xD;
A novel survey item at baseline and 6-weeks post-disclosure asked participants to rate the usefulness of whole genome sequencing results for managing health now on a 1-10 scale.</description>
        <time_frame>Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)</time_frame>
        <population>69 surveys completed at follow-up</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Active-Duty Airmen Cohort</title>
            <description>Ostensibly healthy, active-duty Airmen who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving exome sequencing (ES) undergo ES and have the results returned to them.</description>
          </group>
        </group_list>
        <measure>
          <title>Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing</title>
          <description>Adapted measures assessed participants' attitudes toward genetic information, trust of physicians and the military regarding use of genetic information. (Hall et al. 2006). Scores are summed, with higher scores on a 4-20 scale representing greater trust.&#xD;
A novel survey item at baseline and 6-weeks post-disclosure asked participants to rate the usefulness of whole genome sequencing results for managing health now on a 1-10 scale.</description>
          <population>69 surveys completed at follow-up</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Trust at baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.31" spread="2.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trust at follow-up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.10" spread="2.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Usefulness - Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.76" spread="2.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Usefulness - follow-up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.30" spread="2.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Active-duty Airmen's Health Perceptions</title>
        <description>Assessed using a validated measure of subjective perceptions about health status. (Latham 2013, DeSalvo 2006). Responses are on a 1 - 5 scale, where higher scores indicate more positive responses.</description>
        <time_frame>Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)</time_frame>
        <population>69 surveys were completed at follow-up</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy Active-Duty Airmen Cohort</title>
            <description>Ostensibly healthy, active-duty Airmen who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving exome sequencing (ES) undergo ES and have the results returned to them.</description>
          </group>
        </group_list>
        <measure>
          <title>Active-duty Airmen's Health Perceptions</title>
          <description>Assessed using a validated measure of subjective perceptions about health status. (Latham 2013, DeSalvo 2006). Responses are on a 1 - 5 scale, where higher scores indicate more positive responses.</description>
          <population>69 surveys were completed at follow-up</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Health perceptions- baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.95" spread="0.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Health perceptions - follow-up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.86" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From baseline survey to approximately 6 weeks after disclosure (43 weeks after baseline)</time_frame>
      <desc>Any serious adverse events linked to the disclosure of genomic information will be reported both to the Institutional Review Board (IRB) within one week of the time the event is identified. For all other metrics, the PI will review data &amp; report annually to the IRB.</desc>
      <group_list>
        <group group_id="E1">
          <title>Healthy Active-Duty Airmen Cohort</title>
          <description>Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.&#xD;
Whole exome sequencing: Whole exome sequencing at 125x coverage (i.e., at least 125 sequencing reads covering each position within the exome region of interest) performed at the Laboratory of Molecular Medicine's CLIA certified laboratory on 75 enrolled individuals</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jill Robinson</name_or_title>
      <organization>Baylor College of Medicine</organization>
      <phone>7137985848</phone>
      <email>jill.robinson@bcm.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03276637
org study id: The MilSeq Project
nct id: NCT03276637
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The MilSeq Project is a nonrandomized, prospective pilot study of whole exome sequencing
      (WES) in the U.S. Air Force. The purpose of this study is to explore the implementation of
      WES into clinical medical care in the military health system.
The objective of this effort is to investigate: (a) military healthcare providers' (HCPs')
      genomic knowledge before and after receiving a genomic educational primer and after
      disclosing whole exome sequencing (WES) results to begin to assess the genomic educational
      needs of military HCPs; (b) active-duty Airmen's knowledge and perceptions of genomic
      sequencing (GS); (c) reasons why active-duty Airmen choose to participate, or not to
      participate, in research involving GS; (d) how WES study participants, including HCPs and
      sequenced active-duty Airmen (patient-participants), respond to and use WES results; (e) the
      collection of medical, behavioral, and healthcare utilization outcomes related to the
      clinical integration of WES in the military; (f) how return of WES results and integration
      into the Electronic Medical Record (EMR) do or do not impact perceptions of mission readiness
      and duty assignments. Given the lack of prior research in this area in the Air Force and the
      broad number of topics of interest, the aims of the study are predominantly exploratory and
      results may be hypothesis generating.

      The MilSeq Project will be conducted in two sequential phases. Phase I of the study will
      recruit, consent, and enroll approximately 75 ostensibly healthy active-duty Airmen who
      receive medical care in military Primary Care, Internal Medicine, and/or Family Practice
      settings to take a baseline survey. This survey will be administered to explore active-duty
      Airmen's perceptions of and preferences for GS, identify motivations and barriers to
      active-duty Airmen participating in a WES study, and assess interest in taking part in the
      WES study.

      Phase II of the study will recruit, consent, and enroll 75 ostensibly healthy active-duty
      Airmen who receive medical care in military Primary Care, Internal Medicine and/or Family
      Practice settings who in their baseline survey expressed interest in receiving WES through a
      research study. WES will be performed on each enrolled patient-participant. The result will
      be disclosed by an HCP-participant and permanently integrated into the patient-participant's
      EMR. Phase II will also recruit 10-20 military Primary Care, Internal Medicine, and/or Family
      Practice HCPs and consent them to participate in the study. The HCPs will receive an
      educational primer in genomics and will disclose WES results to Airmen participants.

      There are a number of potential benefits and challenges to incorporating genomic medicine
      into the military, some that are relevant to the broader civilian community, but some that
      are unique to this population. Some of these challenges include: (a) how GS may or may not
      affect the perception of fitness for duty; (b) how genomic discrimination may or may not
      occur in the military setting; (c) how to best deal with unanticipated findings; and (d) how
      genomic results can be practically integrated into a military setting. In this pilot study,
      these potential opportunities and challenges will be explored, which will provide a basis for
      future study and begin to inform decisions regarding clinical care of active-duty service
      members.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.
primary purpose: Health Services Research
masking: None (Open Label)
measure: Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions
time frame: Baseline and 6 weeks post disclosure of genomic sequencing results (approx. 43 weeks after baseline)
description: Assessed using a novel measure of perceptions about use of genetic information for military career duty assignment decisions on a 1-5 scale, where higher scores indicate more positive attitudes.
measure: Genomic Sequencing Findings
time frame: Results disclosure (within 1 month of sequencing completion)
description: Analysis of whole exome sequencing results identified the number of participants with genomic findings, including monogenic disease risk, carrier status, and risk allele presence.
measure: Active-duty Airmen Reported Health Care Utilization Related to Study Results
time frame: 6 weeks post-disclosure (approx. 43 weeks after baseline)
description: Participants' health care utilization was assessed through a combination of medical record reviews and novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS). Survey self-report data were compared to services and procedures indicated on medical record review.
measure: Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing
time frame: Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)
description: Adapted measures assessed participants' attitudes toward genetic information, trust of physicians and the military regarding use of genetic information. (Hall et al. 2006). Scores are summed, with higher scores on a 4-20 scale representing greater trust.
A novel survey item at baseline and 6-weeks post-disclosure asked participants to rate the usefulness of whole genome sequencing results for managing health now on a 1-10 scale.
measure: Active-duty Airmen's Health Perceptions
time frame: Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)
description: Assessed using a validated measure of subjective perceptions about health status. (Latham 2013, DeSalvo 2006). Responses are on a 1 - 5 scale, where higher scores indicate more positive responses.
arm group label: Healthy Active-Duty Airmen Cohort
arm group type: Experimental
description: Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.
intervention type: Genetic
intervention name: Whole exome sequencing
description: Whole exome sequencing at 125x coverage (i.e., at least 125 sequencing reads covering each position within the exome region of interest) performed at the Laboratory of Molecular Medicine's Clinical Laboratory Improvement Amendments (CLIA) certified laboratory on 75 enrolled individuals
arm group label: Healthy Active-Duty Airmen Cohort
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
country: United States
citation: McMorrow D. The $100 genome: implications for the DoD. Technical Report. McLean, Virginia: The MITRE Corporation; 2010.
citation: De Castro M, Biesecker LG, Turner C, Brenner R, Witkop C, Mehlman M, Bradburne C, Green RC. Genomic medicine in the military. NPJ Genom Med. 2016 Jan 13;1:15008. doi: 10.1038/npjgenmed.2015.8. eCollection 2016.
PMID: 29263806
citation: Collins FS, Guttmacher AE. Genetics moves into the medical mainstream. JAMA. 2001 Nov 14;286(18):2322-4. doi: 10.1001/jama.286.18.2322. No abstract available.
PMID: 11710899
citation: Collins FS, Green ED, Guttmacher AE, Guyer MS; US National Human Genome Research Institute. A vision for the future of genomics research. Nature. 2003 Apr 24;422(6934):835-47. doi: 10.1038/nature01626. Epub 2003 Apr 14. No abstract available.
PMID: 12695777
citation: McCarthy JJ, McLeod HL, Ginsburg GS. Genomic medicine: a decade of successes, challenges, and opportunities. Sci Transl Med. 2013 Jun 12;5(189):189sr4. doi: 10.1126/scitranslmed.3005785.
PMID: 23761042
citation: Green RC, Rehm HL, Kohane IS. Clinical genome sequencing. In: Ginsburg GS, Willard HF, eds. Genomic and Personalized Medicine. 2nd ed. San Diego: Academic Press; 2013:102-22.
citation: Christensen KD, Vassy JL, Jamal L, Lehmann LS, Slashinski MJ, Perry DL, Robinson JO, Blumenthal-Barby J, Feuerman LZ, Murray MF, Green RC, McGuire AL; MedSeq Project Team. Are physicians prepared for whole genome sequencing? a qualitative analysis. Clin Genet. 2016 Feb;89(2):228-34. doi: 10.1111/cge.12626. Epub 2015 Jul 7.
PMID: 26080898
citation: Vassy JL, Christensen KD, Slashinski MJ, Lautenbach DM, Raghavan S, Robinson JO, Blumenthal-Barby J, Feuerman LZ, Lehmann LS, Murray MF, Green RC, McGuire AL. 'Someday it will be the norm': physician perspectives on the utility of genome sequencing for patient care in the MedSeq Project. Per Med. 2015;12(1):23-32. doi: 10.2217/pme.14.68.
PMID: 25642274
citation: Vassy JL, Lautenbach DM, McLaughlin HM, Kong SW, Christensen KD, Krier J, Kohane IS, Feuerman LZ, Blumenthal-Barby J, Roberts JS, Lehmann LS, Ho CY, Ubel PA, MacRae CA, Seidman CE, Murray MF, McGuire AL, Rehm HL, Green RC; MedSeq Project. The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine. Trials. 2014 Mar 20;15:85. doi: 10.1186/1745-6215-15-85.
PMID: 24645908
citation: Johnston JJ, Lewis KL, Ng D, Singh LN, Wynter J, Brewer C, Brooks BP, Brownell I, Candotti F, Gonsalves SG, Hart SP, Kong HH, Rother KI, Sokolic R, Solomon BD, Zein WM, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG. Individualized iterative phenotyping for genome-wide analysis of loss-of-function mutations. Am J Hum Genet. 2015 Jun 4;96(6):913-25. doi: 10.1016/j.ajhg.2015.04.013.
PMID: 26046366
citation: Green RC, Lautenbach D, McGuire AL. GINA, genetic discrimination, and genomic medicine. N Engl J Med. 2015 Jan 29;372(5):397-9. doi: 10.1056/NEJMp1404776. No abstract available.
PMID: 25629736
citation: Robinson JO, Carroll TM, Feuerman LZ, Perry DL, Hoffman-Andrews L, Walsh RC, Christensen KD, Green RC, McGuire AL; MedSeq Project Team. Participants and Study Decliners' Perspectives About the Risks of Participating in a Clinical Trial of Whole Genome Sequencing. J Empir Res Hum Res Ethics. 2016 Feb;11(1):21-30. doi: 10.1177/1556264615624078. Epub 2016 Feb 28.
PMID: 26928896
citation: Vassy JL, McLaughlin HM, MacRae CA, Seidman CE, Lautenbach D, Krier JB, Lane WJ, Kohane IS, Murray MF, McGuire AL, Rehm HL, Green RC. A one-page summary report of genome sequencing for the healthy adult. Public Health Genomics. 2015;18(2):123-9. doi: 10.1159/000370102. Epub 2015 Jan 21. Erratum In: Public Health Genomics. 2015 Apr;18(3):191. McLaughlin, Heather L [corrected to McLaughlin, Heather M].
PMID: 25612602
citation: Krier J, McLaughlin HM, Lane WJ, et al. The return of pharmacogenomic variants in the MedSeq Project: reporting approach and physician response. Annual Meeting of the American Society of Human Genetics. Boston, MA2013
citation: Lane WJ, Westhoff CM, Uy JM, Aguad M, Smeland-Wagman R, Kaufman RM, Rehm HL, Green RC, Silberstein LE; MedSeq Project. Comprehensive red blood cell and platelet antigen prediction from whole genome sequencing: proof of principle. Transfusion. 2016 Mar;56(3):743-54. doi: 10.1111/trf.13416. Epub 2015 Dec 3.
PMID: 26634332
citation: Giovanni MA, Krier J, Vassy JL, Lautenbach DM, Green RC, Murray MF. A brief curriculum for physician orientation to clinical whole genome sequencing. American Society of Human Genetics Annual Meeting. Boston, MA2013.
citation: Krier JB, Blout CB, D L, et al. Communication and management of genomic sequencing results by non-geneticist physicians. American Society of Human Genetics; 2015; Baltimore, MD.
citation: Green RC, Goddard KAB, Jarvik GP, Amendola LM, Appelbaum PS, Berg JS, Bernhardt BA, Biesecker LG, Biswas S, Blout CL, Bowling KM, Brothers KB, Burke W, Caga-Anan CF, Chinnaiyan AM, Chung WK, Clayton EW, Cooper GM, East K, Evans JP, Fullerton SM, Garraway LA, Garrett JR, Gray SW, Henderson GE, Hindorff LA, Holm IA, Lewis MH, Hutter CM, Janne PA, Joffe S, Kaufman D, Knoppers BM, Koenig BA, Krantz ID, Manolio TA, McCullough L, McEwen J, McGuire A, Muzny D, Myers RM, Nickerson DA, Ou J, Parsons DW, Petersen GM, Plon SE, Rehm HL, Roberts JS, Robinson D, Salama JS, Scollon S, Sharp RR, Shirts B, Spinner NB, Tabor HK, Tarczy-Hornoch P, Veenstra DL, Wagle N, Weck K, Wilfond BS, Wilhelmsen K, Wolf SM, Wynn J, Yu JH; CSER Consortium. Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine. Am J Hum Genet. 2016 Jun 2;98(6):1051-1066. doi: 10.1016/j.ajhg.2016.04.011. Epub 2016 May 12. Erratum In: Am J Hum Genet. 2016 Jul 7;99(1):246.
PMID: 27181682
citation: Berg JS, Agrawal PB, Bailey DB Jr, Beggs AH, Brenner SE, Brower AM, Cakici JA, Ceyhan-Birsoy O, Chan K, Chen F, Currier RJ, Dukhovny D, Green RC, Harris-Wai J, Holm IA, Iglesias B, Joseph G, Kingsmore SF, Koenig BA, Kwok PY, Lantos J, Leeder SJ, Lewis MA, McGuire AL, Milko LV, Mooney SD, Parad RB, Pereira S, Petrikin J, Powell BC, Powell CM, Puck JM, Rehm HL, Risch N, Roche M, Shieh JT, Veeraraghavan N, Watson MS, Willig L, Yu TW, Urv T, Wise AL. Newborn Sequencing in Genomic Medicine and Public Health. Pediatrics. 2017 Feb;139(2):e20162252. doi: 10.1542/peds.2016-2252. Epub 2017 Jan 17.
PMID: 28096516
citation: Kaphingst KA, Facio FM, Cheng MR, Brooks S, Eidem H, Linn A, Biesecker BB, Biesecker LG. Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet. 2012 Nov;82(5):408-15. doi: 10.1111/j.1399-0004.2012.01909.x. Epub 2012 Aug 7.
PMID: 22694298
citation: Bowling BV, Acra EE, Wang L, Myers MF, Dean GE, Markle GC, Moskalik CL, Huether CA. Development and evaluation of a genetics literacy assessment instrument for undergraduates. Genetics. 2008 Jan;178(1):15-22. doi: 10.1534/genetics.107.079533.
PMID: 18202354
citation: Gray SW, Hicks-Courant K, Cronin A, Rollins BJ, Weeks JC. Physicians' attitudes about multiplex tumor genomic testing. J Clin Oncol. 2014 May 1;32(13):1317-23. doi: 10.1200/JCO.2013.52.4298. Epub 2014 Mar 24.
PMID: 24663044
citation: Selim AJ, Rogers W, Qian SX, Brazier J, Kazis LE. A preference-based measure of health: the VR-6D derived from the veterans RAND 12-Item Health Survey. Qual Life Res. 2011 Oct;20(8):1337-47. doi: 10.1007/s11136-011-9866-y. Epub 2011 Feb 19.
PMID: 21336657
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Robert C. Green, MD, MPH
investigator title: Professor of Medicine, Division of Genetics, Department of Medicine
mesh term: Disease Susceptibility
mesh term: Genetic Predisposition to Disease
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 