Trial Outcomes & Findings for Return of Genomic Results and Aggregate Penetrance in Population-Based Cohorts (NCT NCT04196374)
NCT ID: NCT04196374
Last Updated: 2026-08-03
Results Overview
Living JHS/FHS participants sequenced as part of the TOPMed program who were notified about an actionable genetic result that warranted having the research result verified who followed through with having their result confirmed and disclosed to their health care provider.
COMPLETED
NA
7603 participants
From genetic result notification to 8 months post-disclosure
2026-08-03
Participant Flow
FHS and JHS participants who had a disclosure session to discuss actionable genetic findings that were clinically confirmed.
Participant milestones
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of the TOPMed Program who had an actionable genetic result in a gene on the ACMG v2.0 secondary findings gene list or PALB2 clinically confirmed by the study and returned to the participant.
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|---|---|
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Overall Study
STARTED
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7603
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Overall Study
Individuals Identified With Medically Actionable Variants in ACMG SFv2.0 Plus PALB2
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198
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Overall Study
Consented for Genetic Notification
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80
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Overall Study
Reached and Notified About Research Finding
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71
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Overall Study
Agreed to Return of Results
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62
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Overall Study
Clinically Confirmed and Returned Results
|
48
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Overall Study
COMPLETED
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48
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Overall Study
NOT COMPLETED
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7555
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Data was provided from FHS only
Baseline characteristics by cohort
| Measure |
FHS & JHS Participants Whose Genetic Information Were Analyzed
n=7603 Participants
Framingham and Jackson Heart Study participants who had their genomes sequenced as part of TOPMed and analyzed for actionable genetic results in a gene on the ACMG v2.0 secondary findings list or PALB2.
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|---|---|
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Age, Customized
Age of FHS participants
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67.73 years
n=4197 Participants • Data was provided from FHS only
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Sex: Female, Male
Female
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4419 Participants
n=7603 Participants
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Sex: Female, Male
Male
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3184 Participants
n=7603 Participants
|
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Ethnicity (NIH/OMB)
Hispanic or Latino
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13 Participants
n=7603 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
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7581 Participants
n=7603 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
9 Participants
n=7603 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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1 Participants
n=7603 Participants
|
|
Race (NIH/OMB)
Asian
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1 Participants
n=7603 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=7603 Participants
|
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Race (NIH/OMB)
Black or African American
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3408 Participants
n=7603 Participants
|
|
Race (NIH/OMB)
White
|
4162 Participants
n=7603 Participants
|
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Race (NIH/OMB)
More than one race
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21 Participants
n=7603 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
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10 Participants
n=7603 Participants
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PRIMARY outcome
Timeframe: From genetic result notification to 8 months post-disclosurePopulation: Living JHS/FHS participants sequenced as part of the TOPMed program who were notified about an actionable genetic result that warranted having the research result verified.
Living JHS/FHS participants sequenced as part of the TOPMed program who were notified about an actionable genetic result that warranted having the research result verified who followed through with having their result confirmed and disclosed to their health care provider.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=71 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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Follow Through With Disclosure
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48 Participants
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PRIMARY outcome
Timeframe: From the initiation of bioinformatics analysis to disclosure of confirmed actionable genetic finding (approximately 6 months).Population: Implementation costs included the effort and resources needed to screen the existing genetic data for 7,603 FHS and JHS participants for actionable genetic findings.
We will determine the costs and associated time demands of implementing gRoR using a microcosting approach in which study staff track the amount of time they spend and the resources they use for each step of the protocol. Ranges are based on 50% to 200% of point estimates given variability in wages and prices of services.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=7603 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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Total Costs of Program Implementation
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39568 2025 U.S. Dollars
Interval 19784.0 to 79136.0
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PRIMARY outcome
Timeframe: 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the 12 month follow up survey.
For follow-up medical care, we use a gross costing approach where we apply Centers for Medicare and Medicaid fee schedules to participant-reported referrals and tests.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=25 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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Costs of Follow-Up Care
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517 2025 U.S. Dollars
Interval 0.0 to 4285.0
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SECONDARY outcome
Timeframe: At the time of disclosure of confirmed findings (approximately 3 months after initial results notification)Population: Participants in the FHS cohort whose information were reviewed by a genetics professional to ascertain whether genetic testing or referral had been warranted.
Number of participants with actionable genetic results who, per the judgement of a genetic specialist, had already met clinical criteria for genetic testing based on their personal and family histories of disease.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=30 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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Guideline Compliance
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8 Participants
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SECONDARY outcome
Timeframe: 6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results);1 Year Post-Disclosure Survey (from 1 year to 15 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the self-rated health item on the 6 month or 12 month follow up survey, as appropriate. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
We will examine cases to determine the percentage of individuals who report a new or modified diagnosis attributed to results disclosure.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=32 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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New and Modified Diagnoses
6 month follow up
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1 Participants
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New and Modified Diagnoses
12 month follow up
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1 Participants
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SECONDARY outcome
Timeframe: Post Disclosure Survey (up to 1 month from disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the self-rated health item on the post disclosure survey or 12 month follow up survey, as appropriate. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
A single item of self rated health derived from the SF-12v2.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=37 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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Self-Rated Health
Post-disclosure survey · Poor
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1 Participants
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Self-Rated Health
Post-disclosure survey · Fair
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4 Participants
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Self-Rated Health
Post-disclosure survey · Good
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13 Participants
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Self-Rated Health
Post-disclosure survey · Very good
|
10 Participants
|
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Self-Rated Health
Post-disclosure survey · Excellent
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9 Participants
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Self-Rated Health
12 month follow up · Poor
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1 Participants
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Self-Rated Health
12 month follow up · Fair
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4 Participants
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|
Self-Rated Health
12 month follow up · Good
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8 Participants
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Self-Rated Health
12 month follow up · Very good
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6 Participants
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Self-Rated Health
12 month follow up · Excellent
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6 Participants
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SECONDARY outcome
Timeframe: From disclosure to 1 month post-disclosurePopulation: Chart notes of participants with actionable genetic results that were confirmed and disclosed to their health care provider were reviewed to ascertain whether referrals or services had been recommended during disclosure sessions.
We reviewed chart notes from results disclosure sessions to determine whether referrals or services were recommended in response to genetic findings.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=45 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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Number of Participants With Recommendations to Referrals or Services During Clinical Disclosure Sessions
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31 Participants
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SECONDARY outcome
Timeframe: 1 year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the 12 month follow up survey. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
Health care utilization in response to results disclosure reported by participants in the one year follow-up survey, including referrals, tests and/or procedures, and changes to medications.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=25 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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Health Care Utilization
Referrals
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8 Participants
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Health Care Utilization
Had tests and/or procedures
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16 Participants
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Health Care Utilization
Change in medications
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3 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the 12 month follow up survey. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
A series of standardized yes/no questions that assess whether disclosed genetic information motivated participants to make changes to health behaviors, including diet, exercise, dietary supplements use, alcohol use, stress management, and smoking.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=25 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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Self-Reported Changes to Health Behaviors
Reported at least one change
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6 Participants
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Self-Reported Changes to Health Behaviors
Reported change to diet
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5 Participants
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Self-Reported Changes to Health Behaviors
Reported change to exercise plan
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4 Participants
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Self-Reported Changes to Health Behaviors
Reported changed to vitamin or herbal supplement use
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1 Participants
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Self-Reported Changes to Health Behaviors
Reported change in stress management
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3 Participants
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Self-Reported Changes to Health Behaviors
Reported change in smoking habits
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0 Participants
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Self-Reported Changes to Health Behaviors
Reported change in alchohol use
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0 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the 6 month follow up survey. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
The survey assessed the disclosure-specific impact of information on distress and positive emotions using an adapted 12-item version of the FaCTOR, a validated instrument developed for genomic sequencing that is sensitive to responses to high- and low-risk genetic risk results. Subscales assess negative emotions (range: 3 to 15), positive feelings (reverse-scored, range: 4 to 20), uncertainty (range: 3 to 15), and privacy concerns (range: 2 to 10), with higher scores on each subscale indicating more negative experiences.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=29 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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Disclosure-specific Impact
Negative emotions
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3.7 Mean score on specific subscales
Standard Deviation 1.6
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Disclosure-specific Impact
Positive feelings
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13.3 Mean score on specific subscales
Standard Deviation 4.7
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Disclosure-specific Impact
Uncertainty
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5.9 Mean score on specific subscales
Standard Deviation 2.9
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Disclosure-specific Impact
Privacy concerns
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2.6 Mean score on specific subscales
Standard Deviation 1.3
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OTHER_PRE_SPECIFIED outcome
Timeframe: 6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the satisfaction item on the 6 month or 12 month follow up survey. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
Surveys assessed how helpful participants felt the results disclosure session was using a novel single question.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=32 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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Satisfaction With Disclosure
Response on 6 month follow up survey · Very unhelpful
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0 Participants
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Satisfaction With Disclosure
Response on 6 month follow up survey · Unhelpful
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0 Participants
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Satisfaction With Disclosure
Response on 6 month follow up survey · Mixed
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5 Participants
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Satisfaction With Disclosure
Response on 6 month follow up survey · Helpful
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5 Participants
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Satisfaction With Disclosure
Response on 6 month follow up survey · Very helpful
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19 Participants
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Satisfaction With Disclosure
Response on 12 month follow up survey · Very unhelpful
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0 Participants
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Satisfaction With Disclosure
Response on 12 month follow up survey · Unhelpful
|
0 Participants
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Satisfaction With Disclosure
Response on 12 month follow up survey · Mixed
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1 Participants
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Satisfaction With Disclosure
Response on 12 month follow up survey · Helpful
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13 Participants
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Satisfaction With Disclosure
Response on 12 month follow up survey · Very helpful
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11 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the regret item on the 6 month or 12 month follow up survey. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
Surveys assessed if participants regretted their decisions to receive their genetic findings using a novel single question.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=29 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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Decisional Regret
Number reporting regret on the 12 month follow up survey
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2 Participants
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Decisional Regret
Number reporting regret on the 6 month follow up survey
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0 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the 12 month follow up survey. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
The survey assessed with whether participants shared their genetic information with relatives .
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=25 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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Sharing With Relatives
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24 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the 12 month follow up survey. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
The survey assessed whether participants had relatives that received genetic testing based on disclosure to the participant.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=25 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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Family Testing
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6 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: Post Disclosure Survey (up to 1 month from disclosure of confirmed results); 6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results)Population: Participants with confirmed and disclosed actionable genetic findings who completed the post-disclosure or 6 month follow up surveys. Only living participants identified with actionable genetic results that were confirmed and disclosed to their health care provider were asked to complete surveys.
We measure general anxiety using a 4-item version of the General Anxiety Disorder Scale, a validated scale that allows investigators to identify individuals with a potential mood disorder. Scores range from 4 to 16, with higher scores indicating greater anxiety.
Outcome measures
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=38 Participants
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
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|---|---|
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General Anxiety
Score per post-disclosure survey
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5.8 Score on 4-item GAD
Standard Deviation 3.2
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General Anxiety
Score per 6 month follow up survey
|
5.7 Score on 4-item GAD
Standard Deviation 2.1
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Adverse Events
FHS & JHS Participants With an Actionable Genomic Finding
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
FHS & JHS Participants With an Actionable Genomic Finding
n=71 participants at risk
Framingham and Jackson Heart Study participants who have had their genomes sequenced as part of TOPMed will be notified if an actionable genetic result in an ACMG v2.0 gene is identified and will be offered the opportunity to have their research result clinically confirmed by the study.
Genomic Sequencing: Whole Genome Sequencing and reporting of actionable genomic results for genes included on the ACMG secondary findings list.
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|---|---|
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General disorders
Other Adverse Event
|
2.8%
2/71 • Number of events 2 • From initial contact about a possible genomic finding until the end of follow-up (approximately 15 months after initial notification)
Serious Adverse Events were defined as instances where patients received major interventions (e.g., prophylactic surgery, placement of a pacemaker) based on an erroneous finding. Other adverse events were defined as instances where information had been misstated and corrected (e.g., reporting of a carrier status for a recessive condition as risk for a dominant condition).
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place