TABLE 2.

Major themes, factors of regret, and exemplary quotes.

Theme	Freq		Factor	Freq	Smith's S	Exemplary quotes
Regulatory concerns and trial Specific factors	0.97	MD 1: “There were lots of smart people who designed this trial and looked at the biology and felt like this was an appropriate decision for you. And it was approved by IRB, all these other things, because it's not just you as a doctor doing something random. We presented this trial ad nauseum into groups of experts and the design was careful. I think that would allow me to not be plagued at night by decisional regret.”	Importance of dropped medication	0.50	0.3684	MD 7: “But I guess I would feel less [regret] if it was a more minor switch, like dropping carbo from the HER2 type of regimen, which I perceive as minor, because I know some people will have metastatic recurrence even if they got all the treatment.”
			Trial design	0.44	0.2983	MD 24: “And, hopefully, the study has been thoughtfully designed where there's interim analysis and we can look at our data as we go along. And, I think that's very important in de‐escalation designs.”
			Trial rationale	0.39	0.2524	MD 14: “I think you have to make an objective decision whether the trial makes sense and whether it's what you believe in and then you have to separate the objective decision from emotional decisions.”
			Rigor of the process	0.19	0.0856	MD 8: “That's where the DSMB and the PI can be so helpful to say, “Hi, I know you have been burned. I've asked the DSMB to see if we have any early recurrence. I'm going to look at the data and if there's a problem, I will let you know” and if it was you that told me that, I believe you and trust you to do it.”
Practice of medicine	0.86	MD 14: “Well, I mean, again, when you practice long enough stuff happens to your patients. And I think if you are a good clinician, you care a lot about your patients. You always wonder if how you intersected with their destiny cost them their life. And certainly, clinical trials are space travel. It's dangerous. Does not mean you do not do it. And it does not mean it's not for the bigger good, but I think if you are asking if an astronaut dies along the way and you are in charge of them, it's still painful even if you are expecting it, so sure.”	Recur anyway	0.75	0.3525	MD 1: “Patients recur no matter what we do. And I think in order to continue to march forward and do your job, you sort of take those things a little bit in stride.”
			Nature of clinical trials	0.47	0.2565	MD 4: “So, it's something I have to live with and it's not going to stop me from writing clinical trials or enrolling patients in clinical trials because shit happens.”
			Social importance of trials	0.22	0.0786	MD 7: “Making bigger changes in our regimens is going to get us to where we need to go as a field faster, and it's going to ultimately have a larger impact on the community.”
			Compartmentalization	0.11	0.0508	MD 1: “I think the way that I sort of deal with this and allow myself to sleep at night and go on and be a human being is to try to compartmentalize it and say to myself “I did the best I could and these things happen.”
Oncologist emotions	0.83	MD 17: “Now imagine if you are the one that omitted that. So you will, of course feel, unless you are not human, unless… So I will for any of my patients that relapse, I go and look why. What happened? Did we wait too long to start treatment? Were we treating metastatic disease when we started and think we are doing adjuvant? Should we have done imaging to make sure this was not… So yes, I personally will feel now is that, wrong or right? But that's just a personal feeling about my patients.”	Human nature	0.50	0.3843	MD 12: “I think just by human nature, you are going to feel regrets.”
			Did I do enough?	0.39	0.2569	MD 24: “Because, at least you did not sacrifice the standard. You threw the kitchen sink, and it did not work out. It sucks, but it sounds like you cut a corner and are paying the price.”
			Oncologist mindset and biases	0.39	0.2065	MD 31: “At that point they asked me what I would do and I said, “You're young and I do not think I would do it.” So they did not… Like I said, she had this relapse in the bones… But I did not push that person to do it because they had that path CR and I had that bias and they wanted another child because they are coming of age soon.”
			Second thoughts	0.28	0.1936	MD 12: “I think it gives you second thoughts about how actively you are going to participate in a trial when people relapse.”
			Role of anecdote	0.28	0.1135	MD 13: “Yeah. I had a teacher once who always reminded me that the anecdote was the lowest form of science, but it's almost humanly impossible not to look at a string of successes and failures in a clinical trial and begin to wonder out loud whether the results are what you are seeing.”
			Negative trial	0.17	0.1146	MD 29: “Yeah, the answer to that question would be what the ultimate outcome of the trial was. So, if I knew that in that trial, that the patients did really well, even without therapy, then I'd be less likely to beat myself up.”
Communication	0.69	MD 28: “I think if I've done my job, if I've brought equipoise to the table at the time of the conversation and I've really done my best to make the patient have what I believe to be an informed decision, as informed as it can be, and they are part of the plan and they understand that there's inherent risk, and God forbid the recur, I would not feel that I have done them wrong.”	Right Decision at Time	0.50	0.2519	MD 26: “We did what we thought we should, with the best available information we had at the time.”
			Informed consent	0.33	0.1968	MD 30: “When they signed up for the trial, that was described in the consent form. It was a risk. It was something that was unlikely, but not impossible.”
			Shared decision making	0.33	0.1789	MD 7: “I think it makes me feel a little less bad in that it was a shared decision that we undertook the risk of those unknowns.”
Tailoring to the patient	0.56	MD 31: “And at that point had a path CR, and was still on the fence about having a third child. So that person decided to do Tamoxifen alone after they finished up Herceptin, they gave themselves a year or two to think whether you are going to have a child or not. I thought that was reasonable because they were still at the age where they had to make decisions.”	Disease biology	0.31	0.2024	MD 5: “So for me personally, my recurrences, the early‐stage patients that recur is the worst part of my job. Those are people that you treated with curative intent, and you feel like your treatment wasn't good enough.”
			Better life quality	0.28	0.1055	MD 3: “The other way to think about it is, this person is going to have recurrence and you saved her a year of her life that was so much better than if she'd been getting chemotherapy.”
			Patient characteristics (age, personality)	0.22	0.0801	MD 6: “It all comes back to the personality of the patient. If I feel like the patient is someone who is going to herself have regrets, then I'm going to have regret, yes. So, but that would be the kind of person that I probably would not put on the trial in the first place.”