Skip to main content
SpringerLink
Log in

Beliefs and Values About Gene Therapy and In-Utero Gene Editing in Patients with Hemophilia and Their Relatives

  • Original Research Article
  • Published:
The Patient - Patient-Centered Outcomes Research Aims and scope Submit manuscript

Abstract

Aim

Hemophilia is an inherited disease for which current treatment is noncurative. While gene therapy and gene editing are being researched, we do not know how the hemophilia community perceives them. Herein, we explore the beliefs and values regarding these new therapies in patients with hemophilia and their relatives.

Methods

This qualitative study used phone-based semi-structured interviews on 21 adult English-speaking patients with hemophilia A or B and their parents across the United States during March to July 2019. The study was advertised through different chapters of the Hemophilia Foundation. The interview guide included questions about participants’ prior experience with hemophilia, and included two case scenarios about the use of gene therapy and in utero gene editing, after which participants were asked about their opinions, beliefs, and values on each scenario. We used a grounded theory approach and identified the main themes using an inductive process.

Results

We interviewed 21 participants—12 patients and 9 mothers. Most of them had or were related to a patient with severe disease. The main themes discussed were related to efficacy, safety and financial concerns and insurance coverage for both gene therapy and in utero gene editing. Patients and their parents had expected outcomes in terms of durability of therapy and impact on emotional health and lifestyle changes in the long term. Gene therapy was more accepted among patients with severe and uncontrolled disease. In-utero gene editing was not completely accepted because of safety and ethical issues.

Conclusion

Patients with severe hemophilia perceive gene therapy as a potential cure, while gene editing was more controversial. Patients still have questions that remain to be answered regarding safety and efficacy that should be assessed with long-term follow up studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Curtis R, Baker J, Riske B, et al. Young adults with hemophilia in the U.S.: demographics, comorbidities, and health status. Am J Hematol. 2015;90(Suppl 2):S11–6.

    Article  Google Scholar 

  2. Iannone M, Pennick L, Tom A, et al. Prevalence of depression in adults with haemophilia. Haemophilia. 2012;18(6):868–74.

    Article  CAS  Google Scholar 

  3. Palareti L, Potì S, Cassis F, Emiliani F, Matino D, Iorio A. Shared topics on the experience of people with haemophilia living in the UK and the USA and the influence of individual and contextual variables: results from the HERO qualitative study. Int J Qual Stud Health Well-being. 2015;10:28915.

    Article  Google Scholar 

  4. Pinto PR, Paredes AC, Almeida A. Pain prevalence, characteristics, and impact among people with hemophilia: findings from the first portuguese survey and implications for pain management. Pain Med. 2020;21(3):458–71.

    Article  Google Scholar 

  5. Roosendaal G, Lafeber F. Prophylactic treatment for prevention of joint disease in hemophilia–cost versus benefit. N Engl J Med. 2007;357(6):603–5.

    Article  CAS  Google Scholar 

  6. Chen SL. Economic costs of hemophilia and the impact of prophylactic treatment on patient management. Am J Manag Care. 2016;22(5 Suppl):s126–33.

    PubMed  Google Scholar 

  7. Witkop M, Guelcher C, Forsyth A, et al. Treatment outcomes, quality of life, and impact of hemophilia on young adults (aged 18–30 years) with hemophilia. Am J Hematol. 2015;90(Suppl 2):S3–10.

    Article  Google Scholar 

  8. Cavazza M, Kodra Y, Armeni P, et al. Social/economic costs and quality of life in patients with haemophilia in Europe. Eur J Health Econ. 2016;17(Suppl 1):53–65.

    Article  Google Scholar 

  9. van Dijk K, Fischer K, van der Bom JG, Scheibel E, Ingerslev J, van den Berg HM. Can long-term prophylaxis for severe haemophilia be stopped in adulthood? Results from Denmark and the Netherlands. Br J Haematol. 2005;130(1):107–12.

    Article  Google Scholar 

  10. Wells JR, Gater A, Marshall C, Tritton T, Vashi P, Kessabi S. Exploring the impact of infusion frequency in hemophilia a: exit interviews with patients participating in BAY 94-9027 extension studies (PROTECT VIII). Patient. 2019;12(6):611–9.

    Article  Google Scholar 

  11. Nathwani AC, Davidoff AM, Tuddenham EGD. Advances in gene therapy for hemophilia. Hum Gene Ther. 2017;28(11):1004–12.

    Article  CAS  Google Scholar 

  12. Nathwani AC, Reiss UM, Tuddenham EG, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;371(21):1994–2004.

    Article  Google Scholar 

  13. Pasi KJ, Rangarajan S, Mitchell N, et al. Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A. N Engl J Med. 2020;382(1):29–40.

    Article  CAS  Google Scholar 

  14. Miesbach W, Meijer K, Coppens M, et al. Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood. 2018;131(9):1022–31.

    Article  CAS  Google Scholar 

  15. Rangarajan S, Walsh L, Lester W, et al. AAV5-factor VIII gene transfer in severe hemophilia A. N Engl J Med. 2017;377(26):2519–30.

    Article  CAS  Google Scholar 

  16. George LA, Sullivan SK, Giermasz A, et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med. 2017;377(23):2215–27.

    Article  CAS  Google Scholar 

  17. Hartmann J, Croteau SE. 2017 Clinical trials update: innovations in hemophilia therapy. Am J Hematol. 2016;91(12):1252–60.

    Article  CAS  Google Scholar 

  18. Huai C, Jia C, Sun R, et al. CRISPR/Cas9-mediated somatic and germline gene correction to restore hemostasis in hemophilia B mice. Hum Genet. 2017;136(7):875–83.

    Article  CAS  Google Scholar 

  19. Stephens CJ, Lauron EJ, Kashentseva E, Lu ZH, Yokoyama WM, Curiel DT. Long-term correction of hemophilia B using adenoviral delivery of CRISPR/Cas9. J Control Release. 2019;298:128–41.

    Article  CAS  Google Scholar 

  20. Guan Y, Ma Y, Li Q, et al. CRISPR/Cas9-mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse. EMBO Mol Med. 2016;8(5):477–88.

    Article  CAS  Google Scholar 

  21. Novel Gene-Editing Technique Cures beta-Thalassemia in Utero. A novel peptide nucleic acid-based gene-editing technique using a nanoparticle delivery system seemingly cured beta thalassemia in fetal mice. Am J Med Genet A. 2018;176(10):2052–3.

    Article  Google Scholar 

  22. Alapati D, Zacharias WJ, Hartman HA, et al. In utero gene editing for monogenic lung disease. Sci Transl Med. 2019;11(488):eaav8375.

  23. Leal AF, Espejo-Mojica AJ, Sanchez OF, et al. Lysosomal storage diseases: current therapies and future alternatives. J Mol Med (Berl). 2020;98(7):931–46.

    Article  Google Scholar 

  24. Committee USNIoHRDA. Prenatal gene tranfer: scientific, medical, and ethical issues: a report of the Recombinant DNA Advisory Committee. Hum Gene Ther. 2000;11(8):1211–1229.

  25. Doshi BS, Arruda VR. Gene therapy for hemophilia: what does the future hold? Ther Adv Hematol. 2018;9(9):273–93.

    Article  CAS  Google Scholar 

  26. Vuksanovic D, Green HJ, Dyck M, Morrissey SA. Dignity therapy and life review for palliative care patients: a randomized controlled trial. J Pain Symptom Manage. 2017;53(2):162–170 e161.

  27. Perfetto EM, Burke L, Oehrlein EM, Epstein RS. Patient-focused drug development: a new direction for collaboration. Med Care. 2015;53(1):9–17.

    Article  Google Scholar 

  28. Oehrlein EM, Perfetto EM, Love TR, Chung Y, Ghafoori P. Patient-reported outcome measures in the food and drug administration pilot compendium: meeting today’s standards for patient engagement in development? Value Health. 2018;21(8):967–72.

    Article  Google Scholar 

  29. van Balen EC, Krawczyk M, Gue D, et al. Patient-centred care in haemophilia: patient perspectives on visualization and participation in decision-making. Haemophilia. 2019;25(6):938–45.

    Article  Google Scholar 

  30. Hendriks S, Giesbertz NAA, Bredenoord AL, Repping S. Reasons for being in favour of or against genome modification: a survey of the Dutch general public. Hum Reprod Open. 2018;2018(3):hoy008.

  31. Persaud A, Desine S, Blizinsky K, Bonham VL. A CRISPR focus on attitudes and beliefs toward somatic genome editing from stakeholders within the sickle cell disease community. Genet Med. 2019;21(8):1726–34.

    Article  Google Scholar 

  32. Snure Beckman E, Deuitch N, Michie M, Allyse MA, Riggan KA, Ormond KE. Attitudes toward hypothetical uses of gene-editing technologies in parents of people with autosomal aneuploidies. CRISPR J. 2019;2(5):324–30.

    Article  Google Scholar 

  33. Michie M, Allyse M. Gene modification therapies: views of parents of people with Down syndrome. Genet Med. 2019;21(2):487–92.

    Article  CAS  Google Scholar 

  34. Strauss A. Grounded theory methodology. In: Corbin J, ed. Handbook of qualitative research. SAGE, Thousand Oaks, CA, pp. 273–285.

  35. Cassis FR, Querol F, Forsyth A, Iorio A, Board HIA. Psychosocial aspects of haemophilia: a systematic review of methodologies and findings. Haemophilia. 2012;18(3):e101–14.

    Article  CAS  Google Scholar 

  36. SocioCultural, Research Consultants L. Dedoose Version 8.2.14. Web application for managing, analyzing, and presenting qualitative and mixed method research data. Los Angeles: SocioCultural Research Consultants, LLC; 2016.

  37. Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int J Qual Health Care. 2007;19(6):349–57.

    Article  Google Scholar 

  38. Pierce GF, Coffin D, Committee MotWGTRTPCaO. The 1st WFH Gene Therapy Round Table: Understanding the landscape and challenges of gene therapy for haemophilia around the world. Haemophilia. 2019;25(2):189–194.

  39. Iorio A, Skinner MW, Clearfield E, et al. Core outcome set for gene therapy in haemophilia: results of the coreHEM multistakeholder project. Haemophilia. 2018;24(4):e167–72.

    Article  CAS  Google Scholar 

  40. Nathwani AC, Tuddenham EG, Rangarajan S, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 2011;365(25):2357–65.

    Article  CAS  Google Scholar 

  41. von Mackensen S, Kalnins W, Krucker J, et al. Haemophilia patients’ unmet needs and their expectations of the new extended half-life factor concentrates. Haemophilia. 2017;23(4):566–74.

    Article  Google Scholar 

  42. Lee Mortensen G, Strand AM, Almén L. Adherence to prophylactic haemophilic treatment in young patients transitioning to adult care: a qualitative review. Haemophilia. 2018;24(6):862–72.

    Article  Google Scholar 

  43. von der Lippe C, Frich JC, Harris A, Solbraekke KN. Treatment of hemophilia: a qualitative study of mothers’ perspectives. Pediatr Blood Cancer. 2017;64(1):121–7.

    Article  Google Scholar 

  44. Hoffman-Andrews L, Mazzoni R, Pacione M, Garland-Thomson R, Ormond KE. Attitudes of people with inherited retinal conditions toward gene editing technology. Mol Genet Genom Med. 2019;7(7):e00803.

    Google Scholar 

  45. Schneller JL, Lee CM, Bao G, Venditti CP. Genome editing for inborn errors of metabolism: advancing towards the clinic. BMC Med. 2017;15(1):43.

    Article  Google Scholar 

  46. Kay MA. AAV vectors and tumorigenicity. Nat Biotechnol. 2007;25(10):1111–3.

    Article  CAS  Google Scholar 

  47. Directors Acmg Board Of. Genome editing in clinical genetics: points to consider-a statement of the American College of Medical Genetics and Genomics. Genet Med. 2017;19(7):723–4.

    Article  Google Scholar 

Download references

Acknowledgements

We thank the National Hemophilia Foundation and its local chapters for sharing this research initiative with their members. We would like to thank Alia Memon for her contribution in the coding process. Finally, and most importantly, we also thank the patients and relatives who remain invested in the search for treatment for their life-altering disease and were willing to consider participation in our research.

Author information

Authors and Affiliations

  1. Public Health Genetics, University of Washington, Seattle, WA, USA

    Tania C. Vasquez-Loarte & Deborah J. Bowen

  2. Division of Hematology/Oncology, Department of Pediatrics, University of California San Francisco, 550 16th Street Box 0434, San Francisco, CA, USA

    Tiffany Lin Lucas

  3. Institute for Health and Aging, University of California San Francisco, San Francisco, CA, USA

    Julie Harris-Wai

Authors
  1. Tania C. Vasquez-Loarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiffany Lin Lucas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julie Harris-Wai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Deborah J. Bowen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tiffany Lin Lucas.

Ethics declarations

Funding

The research was supported by gift funds to the Center for Maternal–Fetal Precision Medicine at University of California San Francisco (UCSF).

Conflict of interests

The authors disclose no conflicts of interest during the execution of this study.

Ethics approval

Institutional review board approval was obtained from UCSF where patient contact was occurring prior to initiating research activities.

Consent to participate

Once an interested participant contacted the research team, one interviewer (TL) explained the purpose of the study, the procedures, confirmed eligibility, and obtained informed consent.

Consent for Publication

As part of informed consent for the study, participants gave consent for publication of the data derived from their participation in the research study.

Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors contributions

The project was conceived by corresponding author TL and developed in conjunction with all authors, in particular with methodology expertise by JH-W and DB. The interviews were conducted by TL and coding was done by TV-L and DB. The manuscript was written by TL and TV-L with review and edits by all authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 99 kb)

Supplementary material 2 (PDF 2580 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vasquez-Loarte, T.C., Lucas, T.L., Harris-Wai, J. et al. Beliefs and Values About Gene Therapy and In-Utero Gene Editing in Patients with Hemophilia and Their Relatives. Patient 13, 633–642 (2020). https://doi.org/10.1007/s40271-020-00442-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40271-020-00442-7

Search

Navigation