Enabling Personalized Medicine Through Exome Sequencing in the U.S. Air Force

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The MilSeq Project: Enabling Personalized Medicine Through Exome Sequencing in the U.S. Air Force

Conditions
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Healthy Adults, Genetic Predisposition to Disease

Intervention / Treatment
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* Genetic: Whole exome sequencing


Participation Criteria
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Eligibility Criteria
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Patient-Participant Inclusion Criteria: 18 years or older An active Air Force Airman Fluent in English Seen or eligible to be seen by a provider at Wilford Hall Ambulatory Surgical Center at Joint Base San Antonio (JBSA) Lackland Air Force Base Healthcare Provider-Participant Inclusion Criterion An active or Department of Defense civilian Primary Care, Internal Medicine, or Family Practice Healthcare Provider (Physician, Physician Assistant, or Nurse Practitioner) or resident practicing at Wilford Hall Ambulatory Surgical Center at JBSA Lackland Air Force Base Patient-Participant Exclusion Criteria: Those who do not meet the above inclusion criteria Those with clinically concerning scores on anxiety and distress scales in baseline survey Trainees (basic military training or tech school) Airmen with an active change of duty station order or deployment order and expected to leave San Antonio in 6 months or less Airmen expected to be discharged from the Air Force in 6 months or less Healthcare Provider-Participant Exclusion Criteria: Providers who do not meet the above inclusion criteria Providers with an active change of duty station order or deployment order and expected to leave San Antonio in 6 months or less Providers expected to be discharged from the Air Force in 6 months or less

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Active-Duty Airmen Cohort<br>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. | Genetic: Whole exome sequencing<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions | 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. | Baseline and 6 weeks post disclosure of genomic sequencing results (approx. 43 weeks after baseline) | 
| Genomic Sequencing Findings | Analysis of whole exome sequencing results identified the number of participants with genomic findings, including monogenic disease risk, carrier status, and risk allele presence. | Results disclosure (within 1 month of sequencing completion) | 
| Active-duty Airmen Reported Health Care Utilization Related to Study Results | 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. | 6 weeks post-disclosure (approx. 43 weeks after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing | 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. | Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline) | 
| Active-duty Airmen's Health Perceptions | 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. | Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Whole Genome Sequencing, Whole Exome Sequencing, Military, Air Force, Disease Susceptibility, Genetic Predisposition to Disease, Disease Attributes, Pathologic Processes