A Study of Consent Forms for Whole Exome and Whole Genome Sequencing

Randomized Trial of Consent Interventions for NIH Whole Exome and Whole Genome Sequencing Studies

Background:

The purpose of this study is to investigate the process of consenting participants to whole exome/genome sequencing and its outcomes. It is unknown how best to consent people to this new technology. NO GENOME SEQUENCING IS OFFERED AS PART OF THIS STUDY. This protocol is a companion to other NIH studies that involve genomic sequencing. Participants must be enrolled in a parent NIH study that is collaborating on this consent study to be eligible. Currently this involves only one NIH study.

Objectives:

- To learn the best way to help participants understand sequencing, so they can decide whether to join studies that use it.

Eligibility:

• Adults at least 18 years old who are enrolled in a National Institutes of Health (NIH) study that uses WES/WGS.
• Adults at least 18 years old whose children are enrolled in an NIH study that uses WES/WGS.

Design:

• Participants will take part in the study either in person or over the phone.
• Participants will review two sequencing consent forms with a genetic counselor.
• Before and after meeting with the counselor, participants will answer several questions about sequencing. Each questionnaire will take about 15 minutes.
• Six weeks later, participants will answer questions about sequencing. This will take about 15 minutes.

Study Overview

• Status: Completed
• Conditions: Whole Genome Sequencing

Detailed Description

Consent to participant in studies that include whole exome and whole genome sequencing (WES/WGS) studies and to receive results present challenges to achieving informed consent due to the scope, depth and uncertainty of the information. NIH Intramural studies increasingly involve WES/WGS to identify elusive primary variants. This umbrella protocol aims to compare an evidence-based consent for WES/WGS to a standard consent in collaboration with ongoing and future NIH studies. An equivocal hypothesis will be tested to evaluate whether informed choice and perceptions of uncertainty differ between two consent

groups. A mixed-methods design is proposed that starts with a qualitative mental-model pilot

study to revise an expert opinion consent intervention by integrating lay-person response

preferences. Following development of this evidence-based intervention, a randomized two- factor design will be used for a quantitative survey study conducted in conjunction with a

number of NIH studies conducting WES/WGS to test for differences between two consent

models. A descriptive analysis of the audiotaped consent process will also be conducted to

assess differences in the content or extent of the process, and related outcomes of satisfaction and decisional conflict will also be assessed.

• Study Type: Observational
• Enrollment (Actual): 212

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Parents and eligible children.

Description

• INCLUSION CRITERIA:

Eligible adults (greater than or equal to 18 years of age) consenting to enroll in an NIH study that includes WES/WGS. Parents of eligible children (<18 years of age) consenting to enroll their child(ren) in an NIH study that includes WES/WGS. Participants must be cognitively able to consent and fluent in written and spoken English.

EXCLUSION CRITERIA:

Children (<18 years of age). Non-English speaking participants (until the study has evolved to be able to use translations of the interventions into Spanish).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
WES/WGS; Eligible adults (or parents of eligible children) consenting to enroll in an NIH study thatincludes WES/WGS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A	To contrast the efficacy of an evidence-based streamlined consent model (based upon the integration of an expert opinion model and laypersons responses using a mental- models approach) to a standard NIH consent in consenting adult and parent participants to undergo WES/WGS within NIH Intramural studies.	Ongoing
B	To quantitatively assess changes in understanding, perceptions of uncertainty and informed choice between the two consent interventions, assuming equivalency.	Ongoing
C	To describe satisfaction,decisional conflict and residual questions and concerns following use of each consent intervention.	Ongoing
D	To compare the content, dialogue and time spent in the consent discussions between interventions.	Ongoing

Collaborators and Investigators

• Sponsor: National Human Genome Research Institute (NHGRI)
• Investigators: Principal Investigator: Julie Sapp, National Human Genome Research Institute (NHGRI)

Publications and helpful links

General Publications

• Biesecker LG, Mullikin JC, Facio FM, Turner C, Cherukuri PF, Blakesley RW, Bouffard GG, Chines PS, Cruz P, Hansen NF, Teer JK, Maskeri B, Young AC; NISC Comparative Sequencing Program; Manolio TA, Wilson AF, Finkel T, Hwang P, Arai A, Remaley AT, Sachdev V, Shamburek R, Cannon RO, Green ED. The ClinSeq Project: piloting large-scale genome sequencing for research in genomic medicine. Genome Res. 2009 Sep;19(9):1665-74. doi: 10.1101/gr.092841.109. Epub 2009 Jul 14.
• Ayuso C, Millan JM, Mancheno M, Dal-Re R. Informed consent for whole-genome sequencing studies in the clinical setting. Proposed recommendations on essential content and process. Eur J Hum Genet. 2013 Oct;21(10):1054-9. doi: 10.1038/ejhg.2012.297. Epub 2013 Jan 16.
• Dormandy E, Michie S, Hooper R, Marteau TM. Low uptake of prenatal screening for Down syndrome in minority ethnic groups and socially deprived groups: a reflection of women's attitudes or a failure to facilitate informed choices? Int J Epidemiol. 2005 Apr;34(2):346-52. doi: 10.1093/ije/dyi021. Epub 2005 Feb 28.
• Turbitt E, Chrysostomou PP, Peay HL, Heidlebaugh AR, Nelson LM, Biesecker BB. A randomized controlled study of a consent intervention for participating in an NIH genome sequencing study. Eur J Hum Genet. 2018 May;26(5):622-630. doi: 10.1038/s41431-018-0105-7. Epub 2018 Feb 16.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2013
• Primary Completion (Actual): March 7, 2016
• Study Completion (Actual): November 8, 2021

Study Registration Dates

• First Submitted: August 20, 2013
• First Submitted That Met QC Criteria: August 20, 2013
• First Posted (Estimate): August 23, 2013

Study Record Updates

• Last Update Posted (Actual): November 10, 2021
• Last Update Submitted That Met QC Criteria: November 9, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Informed Consent; WES; WGS
• Other Study ID Numbers: 130171; 13-HG-0171