Genetic Predisposition to Disease, Healthy Adults
Conditions
Keywords
Whole Genome Sequencing, Whole Exome Sequencing, Military, Air Force, Disease Susceptibility, Genetic Predisposition to Disease, Disease Attributes, Pathologic Processes
Brief summary
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
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.
Interventions
GENETICWhole 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
Sponsors
United States Department of Defense
Brigham and Women's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions | Baseline and 6 weeks post disclosure of genomic sequencing results (approx. 43 weeks after baseline) | 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. |
| Genomic Sequencing Findings | Results disclosure (within 1 month of sequencing completion) | Analysis of whole exome sequencing results identified the number of participants with genomic findings, including monogenic disease risk, carrier status, and risk allele presence. |
| Active-duty Airmen Reported Health Care Utilization Related to Study Results | 6 weeks post-disclosure (approx. 43 weeks after baseline) | 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. |
| Military Healthcare Providers' Genomic Literacy | Baseline (pre and post) and Follow-up (follow-up administered approx. 53 weeks after baseline) | Military healthcare provider-participants' genomic literacy were measured with a 14-item measure adapted from the ClinSeq Study (Kaphingst K.A. et al. 2012) administered at baseline, before (pre) and immediately after (post) an education session, and at Follow-up near the end of the study. Items are marked as correct (1) or incorrect (0) and summed for a total scale range of 0 to 14, with higher scores indicating higher genomic literacy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Active-duty Airmen's Health Perceptions | Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline) | 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. |
| Military Healthcare Providers' Confidence With Genomic Data | Baseline (pre and post) and Follow-up (follow-up administered approx. 53 weeks after baseline) | Assessed through a scale developed for the Multiplex initiative to measure provider genomic confidence (Gray SW et al 2014). Scores are summed with higher scores on a 5-20 scale indicating greater confidence in military healthcare provider-participants' abilities to understand genetic information |
| Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing | Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Active-Duty Airmen Cohort 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.
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 | 93 |
| Healthcare Provider Cohort The Healthcare providers who provide medical care in military Primary Care, Internal Medicine and/or Family Practice settings and enroll participants. Military healthcare providers have received a brief genomics training and will return results to the patient-participants | 12 |
| Total | 105 |
Baseline characteristics
| Characteristic | Healthy Active-Duty Airmen Cohort | Healthcare Provider Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 93 Participants | 12 Participants | 105 Participants |
| Age, Continuous | 33.75 years STANDARD_DEVIATION 8.3 | 39 years STANDARD_DEVIATION 9.25 | 34.2 years STANDARD_DEVIATION 8.4 |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic or Lation | 17 Participants | 0 Participants | 17 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Non-Hispanic Other | 13 Participants | 6 Participants | 19 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Non-Hispanic White | 61 Participants | 6 Participants | 67 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Prefer Not to Answer | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 93 participants | 12 participants | 105 participants |
| Sex: Female, Male Female | 45 Participants | 4 Participants | 49 Participants |
| Sex: Female, Male Male | 48 Participants | 8 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 12 |
| other Total, other adverse events | 0 / 75 | 0 / 12 |
| serious Total, serious adverse events | 0 / 75 | 0 / 12 |
Outcome results
Primary
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.
Time frame: 6 weeks post-disclosure (approx. 43 weeks after baseline)
Population: 69 participants completed follow-up survey and several participants selected more than one answer for 83 total responses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Reported Health Care Utilization Related to Study Results | Change in diet | 9 participants |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Reported Health Care Utilization Related to Study Results | Change in exercise | 7 participants |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Reported Health Care Utilization Related to Study Results | Change in use of vitamin supplements | 5 participants |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Reported Health Care Utilization Related to Study Results | Change in use of medication | 5 participants |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Reported Health Care Utilization Related to Study Results | Other change | 1 participants |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Reported Health Care Utilization Related to Study Results | No change | 56 participants |
Primary
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.
Time frame: Baseline and 6 weeks post disclosure of genomic sequencing results (approx. 43 weeks after baseline)
Population: 69 participants completed follow-up survey
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions | Baseline | 2.62 score on a scale | Standard Deviation 0.75 |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions | 6-weeks post-disclosure | 2.66 score on a scale | Standard Deviation 0.91 |
Primary
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.
Time frame: Results disclosure (within 1 month of sequencing completion)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Healthy Active-Duty Airmen Cohort | Genomic Sequencing Findings | Risk Allele findings | Present | 37 Participants |
| Healthy Active-Duty Airmen Cohort | Genomic Sequencing Findings | Monogenic disease findings | Present | 11 Participants |
| Healthy Active-Duty Airmen Cohort | Genomic Sequencing Findings | Monogenic disease findings | Not Present | 64 Participants |
| Healthy Active-Duty Airmen Cohort | Genomic Sequencing Findings | Carrier status findings | Present | 65 Participants |
| Healthy Active-Duty Airmen Cohort | Genomic Sequencing Findings | Carrier status findings | Not Present | 10 Participants |
| Healthy Active-Duty Airmen Cohort | Genomic Sequencing Findings | Risk Allele findings | Not Present | 38 Participants |
Primary
Military Healthcare Providers' Genomic Literacy
Military healthcare provider-participants' genomic literacy were measured with a 14-item measure adapted from the ClinSeq Study (Kaphingst K.A. et al. 2012) administered at baseline, before (pre) and immediately after (post) an education session, and at Follow-up near the end of the study. Items are marked as correct (1) or incorrect (0) and summed for a total scale range of 0 to 14, with higher scores indicating higher genomic literacy.
Time frame: Baseline (pre and post) and Follow-up (follow-up administered approx. 53 weeks after baseline)
Population: Healthcare providers who completed the pre, post and follow-up surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Active-Duty Airmen Cohort | Military Healthcare Providers' Genomic Literacy | Pre test | 9.92 score on a scale | Standard Deviation 1.38 |
| Healthy Active-Duty Airmen Cohort | Military Healthcare Providers' Genomic Literacy | Post test | 11.50 score on a scale | Standard Deviation 1.45 |
| Healthy Active-Duty Airmen Cohort | Military Healthcare Providers' Genomic Literacy | Follow-up | 10.75 score on a scale | Standard Deviation 2.25 |
Secondary
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.
Time frame: Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)
Population: 69 surveys completed at follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing | Trust at baseline | 14.31 score on a scale | Standard Deviation 2.47 |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing | Trust at follow-up | 14.10 score on a scale | Standard Deviation 2.25 |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing | Usefulness - Baseline | 7.76 score on a scale | Standard Deviation 2.11 |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing | Usefulness - follow-up | 7.30 score on a scale | Standard Deviation 2.11 |
Secondary
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.
Time frame: Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)
Population: 69 surveys were completed at follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen's Health Perceptions | Health perceptions- baseline | 3.95 score on a scale | Standard Deviation 0.81 |
| Healthy Active-Duty Airmen Cohort | Active-duty Airmen's Health Perceptions | Health perceptions - follow-up | 3.86 score on a scale | Standard Deviation 0.76 |
Secondary
Military Healthcare Providers' Confidence With Genomic Data
Assessed through a scale developed for the Multiplex initiative to measure provider genomic confidence (Gray SW et al 2014). Scores are summed with higher scores on a 5-20 scale indicating greater confidence in military healthcare provider-participants' abilities to understand genetic information
Time frame: Baseline (pre and post) and Follow-up (follow-up administered approx. 53 weeks after baseline)
Population: Healthcare providers who completed the pre, post and follow-up surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Active-Duty Airmen Cohort | Military Healthcare Providers' Confidence With Genomic Data | Pre-Test | 7.25 score on a scale | Standard Deviation 2.05 |
| Healthy Active-Duty Airmen Cohort | Military Healthcare Providers' Confidence With Genomic Data | Post-Test | 13.00 score on a scale | Standard Deviation 1.41 |
| Healthy Active-Duty Airmen Cohort | Military Healthcare Providers' Confidence With Genomic Data | Follow-up | 12.33 score on a scale | Standard Deviation 2.29 |