Table 2 Global themes, key domains, subthemes, and example belief statements and quotes

 Knowledge

Knowledge gaps about CAR T cell therapy

(barrier)

I would like to know more about toxicity, adverse events, and treatment efficacy. (9)

“So I’d have to think about that a little bit more, but I think a session on side effects and toxicities and complications and how to potentially manage them so that we can counsel patients properly would probably be an important thing to include in a site initiation visit.” - Physician #9

Knowledge gaps about screening procedures (barrier)

I need to know clear eligibility criteria to properly screen for the trial. (9)

“So you need clear eligibility so you know exactly what you’re screening for what the yes’s and no’s are and you’re not wasting anyone’s time in creating false hope… so I think it’s clarity of exactly what is required for the study.” - Physician #12

Knowledge about immunotherapy trials

(enabler)

I am aware of immunotherapy clinical trials for hematological malignancies. (13)

“…there has been approval for CAR T-cell products for B ALL in paediatric patients as well as another CAR T-cell product that’s been approved for aggressive lymphoma. And they’re currently, you know, trying to wrap up to try to make this more available generally speaking outside of clinical trials. ... And people are also trying to develop CAR T-cells outside of the realm of CD-19 antigen therapy so that should actually lead to other availabilities of different CAR T-cell products.” - Physician #3

Information Delivery

(enabler)

I would like to learn about CAR T in person (e.g., rounds, site visits). (5)

“I think presenting the background at our rounds or something is the useful thing.” - Physician #8

 Goals

Concern for Patients (enabler)

CAR T trials are important because they provide patients with more treatment options. (8)

“But more importantly it gives patients an opportunity to access medications and treatments that may not be available for 5, 10, 15, 20 years. So I think it’s really important to put patients on clinical trials and especially for CAR T because… there’s a huge medical need for patients like that that we would actually think of for CAR T. There’s really nothing we can offer those patients.” - Physician #2

Advancing Science (enabler)

Screening for a safety study is important to generate safety data. (4)

“I think there’s still a lot to be learned about it improving both the agent itself and improving management of toxicity. So I would be delighted to contribute to that learning because I do think it’s a big part of the future.” - Physician #12

Support for Trial

(enabler)

Screening for this trial is a priority. (6)

“Well given sort of this is the gold at the end of the rainbow I think we’d still be motivated to get involved.” - Physician #14

Other motivators (enabler)

Trials with inclusive criteria motivate me to participate (1)

“Well easily accessible trials would motivate me because sometimes I do get quite discouraged with certain trials that even though the trials might be open but they have really stringent criteria and even if we screen the patient on an initial screen then they get a second screen and they are rejected. And that just leaves me and my patient with a lot of questions. So an easily accessible trial would really motivate me to enrol my patients because I know that they will make it in.” - Physician #5

 Beliefs about Consequences

Treatment Benefits

(enabler)

This trial presents a possible treatment avenue for patients with very limited options. (12)

“But more importantly it gives patients an opportunity to access medications and treatments that may not be available for 5, 10, 15, 20 years. So I think it’s really important to put patients on clinical trials and especially for CAR T because we just don’t have there’s a huge medical need for patients like that that we would actually think of as CAR T for. There’s really nothing we can offer those patients.” - Physician #2

Advancing Science

(enabler)

This trial will add to the CAR T knowledge base. (4)

“Well obviously the, the benefit is that one adds to the literature, adds to the knowledge on how certain treatments work. So the benefit is that of any research effort is research result.” - Physician #7

Toxicity

(barrier)

CAR T early trials are likely to have high toxicity and mortality rates. (10)

“Well you’d be going through the potential benefits of CAR T-cell therapy also the risks of it and the risks obviously are quite significant with cytokine release syndrome etc.” - Physician #11

Insufficient Evidence

(barrier)

There is not enough data regarding side effects and efficacy. (3)

“We’re only beginning to understand it right now. We don’t know where it’s going to be heading in the next 4-5 years. The early results look really promising but for every patient out there who’s benefited from CAR T therapy there’s a patient conversely who hasn’t benefited from it. And so there’s still lots to learn about it so the disadvantage is that we just don’t have enough information about the long-term outcomes of these patients whether patients are going to be cured of their diseases or not. So there are so many disadvantages that there’s a lack of knowledge right now about the long-term.” - Physician #2

Financial Cost

(barrier)

It is costly to administer CAR T therapy and manage complications. (5)

“Many of them end up in the Intensive Care Unit making it quite an expensive treatment, but at the same time I think it carries along a significant survival benefit for the patients.” - Physician #13

Feasibility and Screening Criteria

(enabler)

The study design and feasibility are important to ensure enough patients are eligible. (7)

“The most important factors [are] a well-designed study, clear eligibility criteria and process for trial conduct. And I guess it also needs to be manageable. … if there were so many tests with inadequate funding to support then that might be something my institution would say this is too expensive. This is too intensive we cannot do it so a feasible screening process and well-designed study would influence me to screen.” - Physician #12

Few Participants

(barrier)

Few patients will be eligible for this trial. (5)

“We generally do need to be able to say from a feasibility perspective that we think we can enrol at least 3 patients onto a study otherwise the workload of opening it is felt not to be worth it for just a very small number of patients.” - Physician #6

 Intention

Intent to Screen

(enabler)

I intend to screen patients for the trial. (14)

“Yeah we’ll be willing and I think it’s not only a matter of choice it’s a need. We need that, it looks like this therapy is quite promising and has potential and most of these patients are in a desperate situation and this is actually, here in Canada, it’s a need. So it’s needed and I think myself, my colleagues, would be happy to have a trial and take part in this and to put subjects first.” - Physician #4

I intend to screen patients for a safety trial. (7)

“Early phase studies here at our centre are harder to conduct ... Well given sort of this is the gold at the end of the rainbow I think we’d still be motivated to get involved.” - Physician #14

Conditional Intent

(barriers)

I would consider whether the patient could commit to the trial. (1)

“If they are not a compliant patient for the study schedule then I will not to include a patient to trial… I rather this person this subject is traded for person who can commit himself or herself to the study protocol.” - Physician #10

 Environmental Context and Resources

Institutional Capacity

(enabler)

My centre has the resources to support a trial. (6)

“So we don’t hit too many hurdles here ourselves and in general if we think we have a good study that we can recruit patients to they [REB] will support us in making that work.” - Physician #12

Access to Funding

(enabler)

Funding is important to keep the study moving forward. (9)

“…it also has to be economically feasible for our clinical trials unit… the clinical trials group has to be responsible in trying to introduce studies that are not gonna drain the budgets for everybody else.” - Physician #8

Access to Study Personnel

(enabler)

Research personnel are needed for a smooth screening process. (8)

“… you have to have a number of research people who are working with you because they’re the ones who need to collect the data. They’re the ones who need to, you know, follow the patients with the physicians and that kind of stuff. So if you have a good research staff then it certainly makes life a lot easier for the physician.” - Physician #3

Our medical staff/clinical trial team is able to screen. (4)

“Yeah, yeah and I know most of the, we’re kind of lucky all of our staff has some medical training and so they would actually go through the screening process in detail.” - Physician #2

Physician Time and Workload

(barrier)

Screening requires a lot of work and resources. (6)

“You can call somebody and say come on down and talk to this patient and look at the chart and see if it fits—the typical study is like that and it would be like this too I think although this is so complex this, this therapy and so expensive and so unusual that one would—this is the it becomes a project.” - Physician #7

Trial Availability

(barrier)

We avoid having competing trials. (8)

“We try not to. So that it’s so we wouldn’t be able to run competing studies for especially in this disease.” - Physician #8

 Beliefs about Consequences

Wait Times

(barrier)

Long wait times for screening and time to treatment may be difficult for patients with aggressive diseases. (8)

“I’m not sure what is the turnaround time for the development of this technology specific for that patient, so the patient could die or deteriorate in that time period. And you have to remember these are people, so say if we are only enrolling people who have multiply relapsed refractory disease then I think it might be a case where the patients are really sick. So I think that might be one of the disadvantages.” - Physician #5

 Memory, Attention and Decision Making

Forgetting to Screen

(barrier)

It is possible to forget to screen for this trial. (5)

“If I’m too much busy or too many patients while I’m running the clinic there I may forget.” - Physician #10

I will not forget to screen for this trial. (9)

“No way [laugh] it’s such an important trial, it would be at the forefront of my mind constantly so no I wouldn’t be concerned about that at all.” - Physician #11

Patient Health

(barrier)

I would need to consider their health status. (6)

“The only time I will think twice about offering them a clinical trial is based on their echo [echocardiogram] performance status, their clinical status, but even then I do mention it to them with a caveat that by the time they get enrolled it might be too late, yeah.” - Physician #5

Treatment Options

(barrier)

I would consider if other treatment options are available. (7)

“Because if I have some other therapies to offer them to get them better, rather than sit and do nothing for 2 weeks until I get an answer whether they’ll be enrolled in the trial or not, then I might decide not to enrol them in the trial.” - Physician #5

 Behavioural Regulation

Salience of Trial Improves Screening Practices

(enabler)

Sending reminders to physicians helps keep screening on track. (6)

“So reminders are very helpful, any kind, that every time we have someone come by and give us a reminder on our clinical trial it tends to improve accrual. So, you know, email reminders or, you know, just a small update on accrual, newsletters, all those things that people use for trials I think are helpful in terms of reminding us.” - Physician #13

Screening patient charts on a regular basis may help us identify patients for a clinical trial (5)

“so there are two ways, one is we meet every week to discuss patients and their care to make sure everything is moving on track and whether there are options for certain patients. And, I think presenting the background at our rounds or something is the useful thing.” - Physician #8

Having committed hematologists to screen for the study will help. (2)

“…heightened awareness by the group rather than and, of course, you have champions for studies such as [this], like there’s the PI and keeps reminding people.” - Physician #7

Involving non-profit organizations can increase exposure and salience. (1)

“There’s a place called CARE or an organization in [city]. And they basically give you the updates of all the trials and they also give you information ... they give it usually to hematologists. So that would be some good places to start right there.” - Physician #6

 Social and Professional Role

Perceptions of Screening Role

(enabler)

It is a physician's responsibility to screen patients for a trial. (15)

“It’s the physician’s responsibility to evaluate patients for a clinical trial if there’s a change in their disease status, right. So, if a patient comes in and they’ve relapsed it’s up to the patient’s physician to say okay what clinical trials do I have for this person. Are they eligible and if they are if they do look eligible then to start the process going to get them enrolled.” - Physician #1

Variable Division of Responsibility

(barrier/enabler)

Screening is done by the physician, clinical research coordinator and medical staff. (13)

“Yeah I think, I think with likely the research nurse who would do the actual screening but, you know, hopefully patients would be, would be referred to the hematologist for consideration and assessment and then, you know, in, in turn the research nurse would become involved in sort of scrutinizing the inclusion and exclusion criteria and establishing candidacy. But I think it would be sort of a combined, you know, collaborative effort between those 2 people.” - Physician #15

It is a shared role amongst physicians to screen patients for a trial. (6)

“And all patients of a certain type will go to one group of physicians. In our institution right now we all see a little bit of everything and that may change but that does mean as a group of clinicians here in [city] sometimes we’re perhaps less thorough at screening than we could be because it’s diluted across multiple physicians.” - Physician #12

I pre-screen. Full screening is usually done by the study PI or Co-PI. (5)

“But if you are not on-service and you don’t know about this patient then it’s, it’s what they tell you and what the for example if you are the expert in a certain type of diseases in a group then it’s up to the other colleagues to ask your opinion and ask if this patient is a potential candidate or not. So to affect this process in the sense that you can’t know all patients in a big program it’s up to other physicians also to be motivated and take part in the trial or at least refer patients to the clinical trial.” - Physician #4

Information Provider Role

(enabler)

I provide patients with enough information to make an informed decision. (5)

“So for example if it’s my patient then I’ll do the initial screening like I said and then they would go to the clinical research team. And the research team would evaluate things and then go through the patient one more time. And if the patient actually consents to the study, then I would come in and I would try and answer more of their questions. And even if they haven’t consented to the study when they’re thinking about it then I’ll still go back and talk to them about it. The idea being to give them as much information as possible as they need in order to make a decision one way or another.” - Physician #2