How voluntary consent may be overlooked in gene editing clinical trials.

Main Article Content

Sharon E. O’Hara, DrPH, MPH, MS Jodi Halpern, MD, PhD


In the United States, advocates have successfully fought for accelerated pathways for FDA approval of novel promissory technologies to address severe unmet medical needs. These pathways can blur the distinction between clinical trials as experiments vs. treatment. In addition, a recent focus on developing individual therapeutics through small clinical trials for people with rare diseases has not included early phases to test safety with healthy human volunteers. Rather, the clinical trials are offered as a therapeutic intervention for those with the targeted genetic condition.

This lack of clarity about the distinction between early-in-human trials and treatment is compounded by the unknowns of innovative promissory technologies, impairing the ability of researchers to convey an accurate and thorough picture of the risks and benefits of participation. In addition, researchers are responsible for ensuring that the potential research subject has understood the information provided about the study and for obtaining informed consent, which is considered valid only under conditions where a person makes a voluntary decision about participation. Scientists’ belief that research subjects may not appreciate what is involved in clinical trials and incentives to recruit participants despite this may create a context in which voluntariness is not fully considered.

When physicians recruit their own patients for clinical trials, the dual role of patient care and trial recruitment may create a communicative context that undermines voluntariness. Physicians may be unaware that the patient’s consent is not truly voluntary for several reasons. One is the normalization of their dual role - both scientists and physicians know they are influential in patients’ decisions. Another is when the physician is convinced of the trial intervention’s benefit as a treatment, despite its experimental status.

In this study, we used qualitative interviews to explore whether and how genome editing scientists and physicians are taking care to ensure research subject voluntariness in the face of potentially irresistible enticements to participate in testing unproven interventions. Moreover, we sought to understand whether the connection between one’s professional role and enrollment of clinical trial subjects influenced how scientists and physicians saw the benefits of trial participation as in the subject's best interests.

Keywords: gene editing clinical trials

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How to Cite
O’HARA, Sharon E.; HALPERN, Jodi. How voluntary consent may be overlooked in gene editing clinical trials.. Medical Research Archives, [S.l.], v. 12, n. 1, jan. 2024. ISSN 2375-1924. Available at: <>. Date accessed: 03 mar. 2024. doi:
Research Articles


1. Sydney Lupkin. Drugmakers are slow to prove medicines that got a fast track to market really work. NPR Shots - Health News from NPR. Published July 22, 2022. Accessed July 28, 2022.

2. Office for Human Research Protections (OHRP). Federal Policy for the Protection of Human Subjects ('Common Rule’).; 2017. Accessed March 21, 2023.

3. 21 CFR Part 50 -- Protection of Human Subjects.; 1980. Accessed March 21, 2023.

4. 21 CFR Part 56 --Institutional Review Boards.; 8975.

5. The Belmont Report. Published January 28, 2010. Accessed April 7, 2017.

6. Grady C. Enduring and Emerging Challenges of Informed Consent. Longo DL, ed. N Engl J Med. 2015;372(9):855-862. doi:10.1056/NEJMra1411250

7. Tam NT, Huy NT, Thoa LTB, et al. Participants’ understanding of informed consent in clinical trials over three decades: systematic review and meta-analysis. Bull World Health Organ. 2015;93(3):186-198H. doi:10.2471/BLT.14.141390

8. Hug K. Understanding voluntariness of consent in first-in-human cell therapy trials. Regenerative Medicine. 2020;15(5):1647-1660. doi:10.2217/rme-2019-0126

9. Nelson RM, Beauchamp T, Miller VA, Reynolds W, Ittenbach RF, Luce MF. The Concept of Voluntary Consent. The American Journal of Bioethics. 2011;11(8):6-16. doi:10.1080/15265161.2011.583318

10. Berghmans R. Voluntary Consent, Normativity, and Authenticity. The American Journal of Bioethics. 2011;11(8):23-24. doi:10.1080/15265161.2011.583323

11. Roberts LW. Informed Consent and the Capacity for Voluntarism. Am J Psychiatry. Published online 2002:8.

12. Bell J, Ho A. Authenticity as a Necessary Condition for Voluntary Choice: A Case Study in Cancer Clinical Trial Participation. The American Journal of Bioethics. 2011;11(8):33-35. doi:10.1080/15265161.2011.583330

13. Hyman J. Voluntariness and Choice. Philosl Q. 2013;63(253):683-708. doi:10.1111/1467-9213.12074

14. Olsaretti S. Freedom, Force and Choice: Against the Rights-Based Definition of Voluntariness. J Polit Philos. 1998;6(1):53-78. doi:10.1111/1467-9760.00046

15. Applebaum P, Roth L, Lidz C, Benson P, Winslade W. False Hopes and Best Data: Consent to Research and the Therapeutic Misconception. The Hastings Center Report. 1987;17(2):20-24. doi:10.2307/3562038

16. Applebaum P, Lidz C, Klitzman R. Voluntariness of Consent to Research: A Preliminary Empirical Investigation. IRB: Ethics & Human Research, The Hastings Center. 2009;31(6):10-14.

17. Horng S, Grady C. Misunderstanding in Clinical Research: Distinguishing Therapeutic Misconception, Therapeutic Misestimation, & Therapeutic Optimism. IRB: Ethics and Human Research. 2003;25(1):11. doi:10.2307/3564408

18. Halpern J, Paolo D, Huang A. Informed consent for early-phase clinical trials: therapeutic misestimation, unrealistic optimism and appreciation. J Med Ethics. 2019;45(6):384-387. doi:10.1136/medethics-2018-105226

19. Applebaum P, Lidz C, Klitzman R. Voluntariness of Consent to Research - A Preliminary Empirical Investigation. doi:

20. Wertheimer A. Voluntary Consent: Why a Value-Neutral Concept Won’t Work. Journal of Medicine and Philosophy. 2012;37(3):226-254. doi:10.1093/jmp/jhs016

21. World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013; 310(20):2191-2194. doi:10.1001/jama.2013.281053

22. Council for International Organizations of Medical Sciences (CIOMS). International Ethical Guidelines for Health-Related Research Involving Humans. Council for International Organizations of Medical Sciences (CIOMS); 2016. doi:10.56759/rgxl7405

23. Kraft SA, Garrison NA. An Ethical Case for Dual-Role Consent: Increasing Research Diversity as a Matter of Respect and Justice. Am J Bioeth. 2019;19(4):44-46. doi:10.1080/15265161.2019.1572816

24. Dekking SAS, van der Graaf R, Zwaan CM, van Delden JJM. Voluntary Informed Consent Is Not Risk Dependent. The American Journal of Bioethics. 2019;19(4):33-35. doi:10.1080/15265161.2019.1572820

25. Morain SR, Joffe S, Largent EA. When Is It Ethical for Physician-Investigators to Seek Consent From Their Own Patients? The American Journal of Bioethics. 2019;19(4):11-18. doi:10.1080/15265161.2019.1572811

26. Grady C. A Hybrid Approach to Obtaining Research Consent. The American Journal of Bioethics. 2019;19(4):28-30. doi:10.1080/15265161.2019.1574493

27. Metselaar S. Commentary 1: Informed Consent of Research Participants: The Gap between Regulations and Reality. Journal of Empirical Research on Human Research Ethics. 2019;14(5):433-435. doi:10.1177/1556264619831589a

28. Cox AC, Fallowfield LJ, Jenkins VA. Communication and informed consent in phase 1 trials: a review of the literature. Support Care Cancer. 2006;14(4):303-309. doi:10.1007/s00520-005-0916-2

29. Halpern J, O’Hara SE, Owen AL, Paolo D. How Scientists Perceive CRISPR’s Translational Promise and the Implications for Individuals with Genetic Conditions. Ethics & Human Research. 2021;43(6):28-41. doi:10.1002/eahr.500108