Table 2.

Decision-Making Factors Related to Future Somatic Gene Editing Clinical Trial Participation

Theme	Subtheme	Quotes
Motivators	Reduce Suffering, Prevent Disease Progression, and Promote Quality of Life	“I think if more research was done, I would consider it. I have suffered a lot from sickle cell, and at this point, I deal with chronic pain. I would do it in the hopes that this illness doesn’t continue to destroy my body.” (Patient) “With sickle cell, I can’t just hop up and run and go do something. I have to think about it, weigh it out. Is it worth my time? Do I really want to do it? Like yesterday, we wanted to go to the pool…Because the sun was starting to go down and the temperature was dropping, I couldn’t just go and jump in the pool because I could go into crisis…sometimes it is hard for me to pick my daughter up when she wants me to.” (Patient) “How it would improve or affect their level of function after? Like on a daily basis. Like patients with sickle cell disease want to know if they will have less painful crises. That they are able to get to work more. Not miss as many school days.” (Physician)
	Altruism	“My participation would only be to benefit my 13-year-old niece. Anything that would make her life different and better than mine was at her age, that would be my only reason to participate.” (Patient) “I think about how can this help all of our children. And so, I would probably be the flip parent and say where do I sign up because I’ve been down this road. I’ve seen what some of my friends have gone through. It can be very dark. It can be very lonely.” (Parent)
	Shortcomings of Current Treatment Options	“I’m not going to lie. If I knew that I could change something in my bone marrow with DNA and not feel pain anymore, I would do it. I don’t want to get chemotherapy, though. That’s probably the one reason why I haven’t already been to the bone marrow transplants.” (Patient) “I don’t think we always think about the social implications that it has, you know, like bone marrow transplant sounds wonderful if it cures your sickle cell disease but nobody talks about the fact that nobody is going to be able to come see you for six months and what that does to a child, you know.” (Parent) “I think of it this way: That my patients have been waiting so long for this. Because there’s such limitations to transplantation.” (Physician)
Deterrents	Permanency of Changing DNA, Uncertainty of Risks and Long-Term Impact	“I’m really talking about changing someone’s DNA. There is always that unintended consequence. You do A, but with the unknown potential?” (Parent) “I think that you have to talk about the fact that a lot of the risks are unknown. We don’t know what is going to happen 20 years from now if we edit your genes when you are a little baby.” (Physician)
	Trial Involvement Burden	“Getting to and from, yeah. How much time is it going to take, even though right now she’s not working, but I am. I’m the only person working in our household.” (Parent) “If the schedule is intense then that may not work with my lifestyle because I wouldn’t want to have to miss days of work and things like that…because I feel like with trials you can’t like miss things.” (Patient) “Some more details about, you know, what would it look like? How many days would they be in the hospital? How sick would they be? How long after would they feel normal again?” (Physician)
	Mistrust of Intent Due to Historical Marginalization	“What is your real reason of researching it? Can I really invent this to, you know, to make some money off of?” (Parent) “‘Oh, look, this person got cured’ But they never tell you about all the people that are still living with just horrible side effects.” (Parent) “You have to think about intent. We have also seen how malicious intent has made advancements go very wrong in our society. There was a question about do you trust your government to do the right thing. Well, I used to.” (Patient)
	Reproduction and Genetic Inheritance	“Families are going to ask…I know many of us have been in the situation where we are talking about transplant and cure, one of the things that you have to discuss, because I don’t think it is intuitive, is that you will still have the ability to pass on the sickle gene.” (Physician) “The other thing that concerns me is that this just fixes the problem for the patient now. What happens when my son has a son, the future generations… I would like to see something that maybe is permanent…” (Parent) “Would you be able to have another child with someone who has sickle cell. Like will this change that? Would that change the whole game up where you can go and do that without having the worry of who you are dating and what they have and everything.” (Patient)
	Concerns over Cost and Access	“If this treatment becomes available to the public, will it be available to everyone equally? I am not rich, but I qualify. I have sickle cell. I struggle with it daily… I don’t want the reason why I can’t get it done is because, oh, your insurance or you don’t have the money.” (Patient) “The companies are all thinking they will make about a million to a million and a half dollars for each procedure I think that the money might be a problem.” (Physician)
Mediators	Religiosity and Spirituality	“If they can go in and snip out this illness and give you a better quality of life, I think God would appreciate that doctor doing that for his child.” (Patient) “I have a child with sickle cell. I have other family members with sickle cell and I still would be on the fence. Because I feel like we’re kind of – we’re playing with God so-to-speak.” (Parent)
	Capacity to Manage Disease and Stage of Life	“Well, being 47, I would want to know what benefit -- like, is this going to extend my life? How -- because I’ve managed now, and I’m comfortable with it for the most part.” (Patient) “I’m sort of at a crossroads. For me to do it, it would be like for me, right now, it would be like – because I’m so used to the pain now and knowing how to control and how to get ahead of it, it would have to be a life or death decision.” (Patient)
Information Desired	Specific Details on Procedure and Clinical Expectations	“I’d also like to know if some things could possibly be reversed …will it correct my vision problems?” (Patient) “How long is the gene is going to hold up for? Do you have to keep going back for some new genes, like, how are they putting it into my body?”(Patient) “A patient needs to know that gene therapy may cure you only if you do it at birth. If you wait until you have already suffered a stroke, renal disease, whatever… even if you have gene therapy, this is not going to reverse the damage that has already occurred.” (Physician)
	Inter-Patient Variability & Rationale Behind Eligibility Criteria	“What are the different results or side effects for the different traits and the different types of sickle cell that you have? (Patient) “Then how do you decide? Like in a family like ours where you have two children with sickle cell disease. When they were both a part of the sickle cell trial, and one got the treatment and the other did not. That wasn’t that big a deal, but in something like this, that is more of a big deal.” (Parent)
	Track Record of Research	“What made it effective? How many rats did they use based on this type? How many humans did they use on this type?” (Patient) “Chances of success, chances of failure, chance of death, chance of irreversible complications, known possible things that could go wrong. How many people have been through this already?” (Physician) “There’s a saying, there’s proof in the pudding. I want you to show me evidence and your findings and your result, whether it’s 25 percent, 50 percent.” (Parent)