Returning incidentally discovered Hepatitis C RNA-seq results to COPDGene study participants

Edwin K Silverman; Arthur Y Kim; Barry J Make; Elizabeth A Regan; Jarrett D Morrow; Craig P Hersh; James O'Brien; James D Crapo; Nadia N Hansel; Gerard Criner; Eric L Flenaugh; Douglas Conrad; Richard Casaburi; Russell P Bowler; Nicola A Hanania; R Graham Barr; Surya P Bhatt; Frank C Sciurba; Antonio Anzueto; MeiLan K Han; Charlene E McEvoy; Alejandro P Comellas; Dawn L DeMeo; Richard Rosiello; Jeffrey L Curtis; Tricia Uchida; Carla Wilson; P Pearl O'Rourke

doi:10.1038/s41525-023-00379-4

Returning incidentally discovered Hepatitis C RNA-seq results to COPDGene study participants

NPJ Genom Med. 2023 Oct 31;8(1):36. doi: 10.1038/s41525-023-00379-4.

Authors

Edwin K Silverman^{1

2}, Arthur Y Kim³, Barry J Make⁴, Elizabeth A Regan⁴, Jarrett D Morrow⁵, Craig P Hersh^{5

6}, James O'Brien⁴, James D Crapo⁴, Nadia N Hansel⁷, Gerard Criner⁸, Eric L Flenaugh⁹, Douglas Conrad¹⁰, Richard Casaburi¹¹, Russell P Bowler⁴, Nicola A Hanania¹², R Graham Barr¹³, Surya P Bhatt¹⁴, Frank C Sciurba¹⁵, Antonio Anzueto¹⁶, MeiLan K Han¹⁷, Charlene E McEvoy¹⁸, Alejandro P Comellas¹⁹, Dawn L DeMeo^{5

6}, Richard Rosiello²⁰, Jeffrey L Curtis^{17

21}, Tricia Uchida²², Carla Wilson²², P Pearl O'Rourke²³

Affiliations

¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. [email protected].
² Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. [email protected].
³ Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Department of Medicine, National Jewish Health, Denver, CO, USA.
⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Division of Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
⁸ Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, PA, USA.
⁹ Pulmonary and Critical Care and Interventional Pulmonary Medicine, Morehouse School of Medicine, Atlanta, GA, USA.
¹⁰ Department of Medicine, University of California San Diego, La Jolla, CA, USA.
¹¹ Rehabilitation Clinical Trials Center, Division of Respiratory and Critical Care Physiology and Medicine, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹² Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA.
¹³ Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY, USA.
¹⁴ Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁵ Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁶ Pulmonary and Critical Care, University of Texas Health, and South Texas Veterans Health Care System, San Antonio, TX, USA.
¹⁷ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, USA.
¹⁸ HealthPartners Institute, Bloomington, MN, USA.
¹⁹ Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospital and Clinics, Iowa City, IA, USA.
²⁰ Department of Pulmonary and Critical Care, Reliant Medical Group, Worcester, MA, USA.
²¹ Medical Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
²² Research Informatics Services, National Jewish Health, Denver, CO, USA.
²³ Harvard Medical School (retired), Boston, MA, USA.

Abstract

The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed and obtained IRB approval for a process of returning HCV research results and an HCV Follow-Up Study questionnaire to capture information about previous HCV diagnosis and treatment information and participant reactions to return of HCV results. During phone calls following the initial HCV notification letter, 84 of 124 participants who could be contacted (67.7%) volunteered that they had been previously diagnosed with HCV infection. Thirty-one of these 124 COPDGene participants were enrolled in the HCV Follow-Up Study. Five of the 31 HCV Follow-Up Study participants did not report a previous diagnosis of HCV. For four of these participants, subsequent clinical HCV testing confirmed HCV infection. Thus, 30/31 Follow-Up Study participants had confirmed HCV diagnoses, supporting the accuracy of the HCV research test results. However, the limited number of participants in the Follow-Up Study precludes an accurate assessment of the false-positive and false-negative rates of the research RNA sequencing evidence for HCV. Most HCV Follow-Up Study participants (29/31) were supportive of returning HCV research results, and most participants found the process for returning HCV results to be informative and not upsetting. Newly diagnosed participants were more likely to be pleased to learn about a potentially curable infection (p = 0.027) and showed a trend toward being more frightened by the potential health risks of HCV (p = 0.11). We conclude that HCV results identified incidentally during transcriptomic research studies can be successfully returned to research study participants with a carefully designed process.

Abstract

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