South-seq: Deoxyribonucleic Acid (DNA) Sequencing for Newborn Nurseries in the South

• ClinicalTrials.gov Identifier: NCT03842995
• Recruitment Status: Recruiting
• First Posted: February 15, 2019
• Last Update Posted: November 30, 2023
• Sponsor: University of Alabama at Birmingham
• Collaborators: University of Mississippi Medical Center; HudsonAlpha Institute for Biotechnology; Woman's Hospital, Louisiana; Children's Hospital of New Orleans; Norton's Children's Hospital; University of Louisville
• Information provided by (Responsible Party): Maria Danila, MD, MSc, MSPH, University of Alabama at Birmingham

Tracking Information

• First Submitted Date: February 13, 2019
• First Posted Date: February 15, 2019
• Last Update Posted Date: November 30, 2023
• Actual Study Start Date: April 15, 2019
• Actual Primary Completion Date: May 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 13, 2019)

Evaluate parental empowerment using the Genetic Counseling Outcome Scale (GCOS) [ Time Frame: From collection of specimen through 3 months ]

Collected after return of whole genome sequencing results using the GCOS. The GCOS is a 24-item counseling outcome scale to assess parental empowerment through questions addressing five constructs: Decision control, Cognitive control, Behavioral control, Emotional regulation, and Future orientation. Each of the 24-items is answered with a 7-point Likert-type scale: Strongly disagree (1), Disagree (2), Slightly disagree (3), Neither agree nor disagree (4), slightly agree (5), agree (6), and strongly agree (7). Range of possible scores for those completing all items: 24-168.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 13, 2019)

• Evaluate parental uncertainties using the Parental Perceptions of Uncertainties in Genomic Sequencing (PUGS) [ Time Frame: From collection of specimen through 3 months ]
  Collected after return of whole genome sequencing results using the PUGS. PUGS is an 8-item scale to assess uncertainties within three domains: Clinical, Affective, and Evaluative. Each of the questions is answered on a 5-point Likert-type scale: Very uncertain (1) to very certain (5). Range of possible scores for those completing all items: 8-40.
• Evaluate personal utility using the Parental Personal Utility Scale (PrU) [ Time Frame: From collection of specimen through 3 months ]
  Collected after return of whole genome sequencing results using the PrU. This measure consists of 17 items answered with a 7-point Likert-type scale: Not at all useful (1), A little useful (2), Somewhat useful (3), Neutral (4), Useful (5), Very useful (6), and Extremely useful (7). Range of possible scores for those completing all items: 17-119.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: South-seq: Deoxyribonucleic Acid (DNA) Sequencing for Newborn Nurseries in the South
• Official Title: South-seq: DNA Sequencing for Newborn Nurseries in the South
• Brief Summary: 2,000 infants with signs suggestive of a genetic disorder being treated at a neonatal intensive care unit (NICU) in which African-American and rural populations are highly represented will be enrolled. Whole genome sequencing (WGS) will be used to identify pathogenic variation in DNA from these infants. Stakeholders, including parents, clinicians, and community leaders, will be engaged to develop culturally adapted educational materials and to equip non-genetics providers to return WGS results. Parents will be provided with these materials through a web portal, the Genome Gateway, and will be placed into one of two arms of a randomized trial to compare the effectiveness technology-assisted WGS result delivery by non-genetics providers relative to result delivery from genetic counselors.

Detailed Description

Barriers to widespread and routine implementation of WGS-enabled clinical care exist at several levels. Surveys of clinicians indicate discomfort in their understanding of genomics and ability to communicate results to patients, and also concern about the time required to do so. Medical geneticists and genetic counselors are disproportionately concentrated in large academic centers, and their numbers are inadequate to support the number of patients that may benefit from WGS. This limitation will have a disproportionate effect on patients in rural and/or medically underserved areas. For example, all but one of the genetic counselors in Alabama are based in Birmingham or Huntsville (lone exception is in Mobile), which means that the southern 2/3 of the state, including major rural underserved areas, have little to no local access to genetic counseling services.

These barriers are especially apparent in neonatal care. For parents of sick neonates, their first interactions with the healthcare system take place in the NICU. Neonatology training traditionally emphasizes critical care and can neglect communication, with one study reporting that 93% of fellows stated that their training in this area should be improved. There is a particular lack of training in genomic neonatal medicine, with few didactic lectures, role play sessions, simulated experiences, or hands on training in clinically relevant scenarios. When infants are diagnosed with congenital anomalies in utero, prenatal consultation with subspecialists can be confusing for genetic conditions with a spectrum of causes and outcomes, and inconsistent information given by different providers, e.g., the neonatologist and the pediatric surgeon.

A central premise underlying the proposal is that non-genetics health care providers, including those outside of academic medical centers, can be empowered to use WGS-testing in their practices. There is ample precedent for implementation of complex technology in primary care: pediatricians, internists, and family practitioners routinely use advanced imaging technologies without a deep understanding of the underlying technology. Bringing WGS-enabled genomic medicine to community health care providers requires, at the least, straightforward criteria to identify patients who may benefit, a user-friendly consent process, clearly worded laboratory reports, easily accessible patient education materials, ready access to support from medical geneticists and genetic counselors, and basic training in how WGS can be applied routinely. The study investigators seek to demonstrate that, if these factors are provided, WGS can be carried out and relevant results returned by newborn medicine providers, and that the patient experience will be at least equal to that achieved with the traditional approach of face-to-face counseling by a geneticist or genetic counselor.

In order to compare technology-assisted WGS result delivery by trained healthcare providers to formal genetic counseling by genetic counselors (standard of care), a series of surveys have been developed and will be completed online using the Genome Gateway platform/website developed for this trial. The survey time points are enrollment (specimen collection from the infant/proband), return of results (ROR) (roughly 2-3 months post-enrollment when WGS results are available), 1-month post-ROR counselling, 4-months post-ROR counselling, and 4.5 months post-ROR counselling.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Health Services Research
• Condition: Whole Genome Sequencing

Intervention

• Behavioral: Genetic Counselor
  Standard of Care
• Behavioral: Trained Healthcare Provider
  Neonatologists and Neonatology Nurse Practitioners that receive training to deliver whole genome sequencing results

Study Arms

• Placebo Comparator: Genetic Counselor
  Standard of Care. Parents/caregivers of neonates enrolled in SouthSeq will receive counseling on their child's Whole Genome Sequencing (WGS) results from Genetic Counselors
  Intervention: Behavioral: Genetic Counselor
• Experimental: Trained Healthcare Provider
  Healthcare providers (e.g., neonatologists and neonatology nurse practitioners) will receive training to competently deliver Whole Genome Sequencing results to parents/caregivers of neonates enrolled in SouthSeq
  Intervention: Behavioral: Trained Healthcare Provider

Publications *

• Biesecker BB, Woolford SW, Klein WMP, Brothers KB, Umstead KL, Lewis KL, Biesecker LG, Han PKJ. PUGS: A novel scale to assess perceptions of uncertainties in genome sequencing. Clin Genet. 2017 Aug;92(2):172-179. doi: 10.1111/cge.12949. Epub 2017 Jan 30. Erratum In: Clin Genet. 2018 May;93(5):1119.
• Costal Tirado A, McDermott AM, Thomas C, Ferrick D, Harris J, Edwards A, McAllister M. Using Patient-Reported Outcome Measures for Quality Improvement in Clinical Genetics: an Exploratory Study. J Genet Couns. 2017 Oct;26(5):1017-1028. doi: 10.1007/s10897-017-0079-6. Epub 2017 Mar 9.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 13, 2019): 800
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2024
• Actual Primary Completion Date: May 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Parents/caregiver/guardian of a newborn (proband) who meets the inclusion criteria in Specific Aim 1
• Parent or caregiver/guardian is willing to participate and answer surveys

Exclusion Criteria:

• Proband has secondary findings from WGS
• Parent or caregiver is not available to participate and answer surveys
• Parent or caregiver requires language interpreter services/translated materials

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Jeffrey Foster, MPH; 205-996-6086; pjfoster@uabmc.edu

Contact: Joshua Melnick; 205-975-0583; jmelnick@uabmc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03842995
• Other Study ID Numbers: IRB-300000328
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Maria Danila, MD, MSc, MSPH, University of Alabama at Birmingham
• Original Responsible Party: Kenneth Saag, MD, MSc, University of Alabama at Birmingham, Principle Investigator
• Current Study Sponsor: University of Alabama at Birmingham
• Original Study Sponsor: Same as current

Collaborators

• University of Mississippi Medical Center
• HudsonAlpha Institute for Biotechnology
• Woman's Hospital, Louisiana
• Children's Hospital of New Orleans
• Norton's Children's Hospital
• University of Louisville

Investigators

• Study Director: Maria Danila, MD, MSc,MSPH; University of Alabama at Birmingham

• PRS Account: University of Alabama at Birmingham
• Verification Date: November 2023