Table 2

Illustrative quotes for qualitative themes for advancing cSLE research

Expanding disease knowledge
Genetics and environmentQ1“It would be very nice down the road if we can identify the patient early in the course of the lupus development – probably people are talking about preclinical – means before you have the full blown picture of lupus skin, are we able to identify those patient and say probably because of your genetic marker and the symptoms that we’re seeing, this might evolve into lupus down the road and it would be ideal if we have medication to stop this from happening at the preclinical levels.” —Expert AA
Q2“You look at all of their gene expression, all of their immune profiles, all of their phenotypes or clinical presentations in the very beginning after treatment and during maintenance and figure out who are the different types of the people, which ones respond to which treatments…knowing ahead of time, like targeting which immune pathway works for what group of patients. Because that would help you, A, personalize the treatment, but also, B, potentially look for new treatment targets like drug targets, specifically.” —Expert BB
Q3“Like this molecular fingerprint needs Cytoxan right away and this molecular fingerprint does best with MMF…And there’s molecular reasons why these pathways are selected. I think that’s where things are going.” —Expert E
Q4“So, this idea of adverse childhood events and the impact of trauma, violence, and chronic stress on the hypopituitary axis in the way that increases the risk for autoimmunity, but also worsen the outcomes and the way mental health plays into that. So, I think there are probably some disease modifying factors that include kind of the psychosocial realm and the environment that…probably are very rich for improving outcomes.” —Expert B
Need for biomarkersQ5“There is always room for improvement in biomarkers that would allow us to identify which patients would have certain organ involvement, which patients would have more severe disease course. So, kind of a biomarkers for assessment of disease severity, not just activity and damage.” —Expert U
Q6“But if you asked me to prioritize, I would say biomarkers, looking at precision-based treatments based on pathophysiology, and then sorting through clinical phenotypes.” —Expert B
Q7“So early identification of [neuropsychiatric] problems is key. Because then you can follow up on the cognitive function over time and determine if is this getting worse, getting better? Is it related to disease activity or not? Or is cognitive impairment an irreversible kind of status that we can change it over time? There are a lot of questions related to cognitive impairment that need to be answered.” —Expert AA
Clinical trialsQ8“A lot of our treatment is still guided by research that is being done on adults that the conclusions of which have sort of been superimposed and assumed to apply to a pediatric population which may or may not be the case. There are still a dearth of clinical trials that are being done in pediatric lupus, though more probably over the last decade than ever before but still very few.” —Expert Q
Q9“We can spend all our money and time discovering these things, but if they’re not palatable and if they – unfortunately, most lupus medicines take a while to work, and so you’re not feeling better for a whole month after taking this medicine and it’s like, what am I doing this for?” —Expert V
Longitudinal outcomesQ10“I would have a longitudinal electronic database where every new onset-lupus patient got entered in, demographic data, family history and got urine and blood samples and then every follow-up visit – the same thing with a blood and urine sample was collected and stored. And so, we would have really on a whole bunch of patients a lot of clinical and molecular data to really understand what was going on and response to medications.” —Expert E
Q11“I think it’s still sort of in its early phases in terms of the kind of longitudinal data that the CARRA registry has on lupus patients. But it will be a very, very powerful tool in the years to come to answer some of those questions.” —Expert Q
Q12“I think because often [young adults with lupus] change services and often cities, so you don’t get all the doctors from the beginning and they even lose follow up…mostly I would say it’s difficult in getting access to data because you don’t have all the information, but when they are adults you don’t have all the information from when they were kids.” —Expert O
Investigator collaboration
Multicentre collaborationQ13“20 years ago, there wasn’t such a thing as a multi-PI R01 and now there is because everybody recognizes now that you really have to do collaborative research in certain fields, that it’s just not possible to do it otherwise.” —Expert X
International priorities and collaborationQ14“If you talk to the people in India or in South America or in Africa about lupus, they will give you different answers [about priorities]. They don’t have the expensive drugs. They have an insane high burden of TB and other infections. They have poor health literacy and access to care. They have slightly different priorities…obviously, we care about the global health of kids with lupus. So somehow it has to come into it.” —Expert G
Q15“I think that North American and European collaboration could be better…we collaborate more on the, let’s say, the general aspects of the disease. But for certain, let’s say, biomarker studies, genetic studies, of course there is always room for improvement for transatlantic collaboration.” —Expert U
Multidisciplinary collaborationQ16“And that instead of producing research that simply deals with clinical rheumatology, people are exploring aspects of the disease that require the expertise of all these other disciplines and looking at things in a more – looking at this very complicated disease in a more nuanced and a deeper way.” —Expert Q
Q17“They’re going to get done by team science, right? A clinician putting the phenotype together, paired with a translational scientist who has a PhD who knows how to design the right experiments, so that we’re doing this in the best quality, highest yield way.” —Expert B
Q18“I guess myself, what my interest is in is trying to get to the basic understanding…of what causes this immune dysregulation in lupus. And so, I think you do need collaboration between geneticists and molecular biologists, immunologists and clinicians who can all come together to really understand what lupus is from their own perspectives but also in a dialogue with each other so that you can move forward.” —Expert V
Relationship with pharmaceutical industryQ19“So better alignment of the pharmaceutical companies’ motivations and needs with the FDA’s perspective…and with the clinicians’ desires and patients’ desires in terms of the drugs, is important…So that all falls under the area of policy and money and prioritization – advocacy.” —Expert G
Partnering with patients and families
Recruiting and engaging patientsQ20“Our clinics are very, very busy…When you have that kind of pace, it’s hard to spend the time that you need to really involve the family and give the feeling that we’re all on the same team.” —Expert K
Q21“It is easier to participate in studies for the person who speaks English, the person who has technology available to them, the person who has time to be on calls during working hours when we’re having our calls. But the person who doesn’t speak English or…can’t get away from their job to get on a phone call at 10:00…we’re not good at engaging them.” —Expert G
Q22“Often times consent for studies are done with [a teen’s] parents in the room and it’s really important to allow that teen to have that conversation confidentially without their parents there…you want the teen to feel empowered and they’re more likely to participate if they feel like this is really about them and their answers count and whether or not they can choose to consent or not and it’s not something they have to do because their parents tell them to or want them to.” —Expert T
Q23“My recommendation would be engaging the patient at different levels of your project because your project has different phases. It starts from the conceptualization of the idea and again you move on with phase one, phase two – application, analysis, interpretation – until you get to publication and dissemination.” —Expert AA
Including outcomes important to patientsQ24“I think that PROs give you a different perspective on how to assess outcomes and especially in the diseases…where we don’t actually know how to measure whether somebody’s in remission…So just because somebody’s protein goes away, does that really mean their lupus is in remission? And in a setting where the doctors are not 100 percent sure how to measure it, it seems to me it’s even more important for us to be listening to how patients might measure it.” —Expert X
Q25“I think there’s a need for more patient-reported outcome measures to…hear from the adolescent about what they feel measures of success would be. …So, for example, I would say that the teenagers are more interested in achieving success in terms of functional outcomes. So, ability to participate in the way they want in school, in sport, in other extracurricular activities, to be able to secure a job without feeling limited by their illness, making sure socially they’re okay, emotionally from a mental health perspective that they’re okay.” —Expert T
Improving care to optimise research
Quality improvement: intersection of healthcare delivery and outcomesQ26“One of the goals of the CARRA registry was to be able to define variation across these centers. And to say, center X is doing really great, what are they doing, versus center Y, which is maybe – has even better outcomes, and what are they doing? So that we can share learning and develop new research studies to try to improve care.” —Expert I
Q27“So things as simple as are we documenting whether or not they got their – even their primary vaccinations? And if so then another project is how we make sure that they get a pneumococcal vaccine because they need to have one, because – to protect them…We’re looking at detecting vascular necrosis early. Detecting osteoporosis early. What do we implement that helps us to detect these things, and if so what kinds of treatment or prophylaxis do we offer patients?… How do we make sure that patients are having their lipids checked every year? And how do we ensure that we’re looking for growth changes?… Can’t use QI to look at which drug treatment is the best, or is the new drug better than what we have? But we certainly use QI to make changes every day in how we take care of patients.” —Expert G
Q28“I should just say the family – what’s happened with that kid’s support and what the family is doing intersects with what the healthcare delivery system is doing, is really important in how well a kid does – not only psychosocially, but also medically. And so, maybe if we can’t cure the disease – I mean, we sometimes say, until we know how to cure and until we have drugs that work better, let’s at least make sure that we use optimally what we have…So I think that’s a place for high impact.” —Expert G
Optimising mental healthQ29“I’d also put money into a patient navigator…somebody to go into our patients’ homes and practice medicine in their environment, as opposed to in our environment…because if you have the navigators in these homes, and you’re making sure they are getting to the appointments, so then we have data [collected during home visits] and we are able to shoot it out of EPIC into like some bioinformatic platform.” —Expert L
Q30“I also think that sometimes people just sort of change what they’re doing because they’re just worried about their patient, but their patient’s actually okay and they can keep going with the protocol. I just get a sense with some of these protocols – and maybe I’m wrong. But I worry because there’s no oversight, really.” —Expert F
Q31“…there are people on our research team that specialize in doing quality assessments of protocol adherence – for example, and making sure that when we’re applying a tool like a SLEDAI score that we’re accurately scoring it or that when we’re enrolling a patient in a prospective study that we’re actually seeing them the proper number of times per year and that we’re not missing ordering specific labs that are in the protocol.” —Expert M
Q32“We don’t currently have a good way to, A, figure out is it from having a chronic illness and not having good resiliency to cope with it, or is it the disease itself that’s causing it…And then we also don’t know how to provide the necessary services.” —Expert BB
Q33“I think we still have many unanswered questions in terms of how the psychological stress of the disease or life impacts the disease and how that impacts patient outcomes in the long term and whether there are areas that we could target in young adulthood and adolescence and childhood that we’re not doing a great job of targeting right now that could have long-term effects on patient outcomes in lupus and in their lives in general.” —Expert Q
Q34“[Anxiety and depression] are common just because you’re a teenager, but also complicated by the fact that they have a chronic condition that they’re having to wrap their head around and that this isn’t gonna go away…it’s very clear that…resources or therapy or medications for mood-related things, there’s a strong appetite for that.” —Expert T
Improving adherence and transition to adult careQ35“And at least identifying when there’s not adherence and getting over the connotation of non-adherence as being a bad thing and making sure that our patients and our research subjects understand that we’re asking them to adhere and we’re needing to earn their adherence as opposed to expecting their compliance – so to speak.” —Expert M
Q36“I think if you could take a cohort of adolescents who are getting treatment for serious lupus…and you could study them and ask about health outcomes, over a ten-year period, and understand what contributes to medication adherence and what contributes to resilience and successful transition to adulthood in a work environment, I think that would be huge.” —Expert N
Q37“And when [patients transitioning to adult care] lose us as their family support, things just don’t go well. So, how do you instill that kind of knowledge and self-care in these patients who don’t know how to do that or don’t understand what it means?” —Expert F
Overcoming investigator barriers and identifying opportunities
Protected timeQ38“As physicians, our time gets sort of fractionated into these teeny little pieces like three days a week we’re in clinic all day…. And then the other days you get pulled into meetings, things appear on your calendar. There’s almost no space to think and write and be creative. And, without that, I don’t think we can move this work forward.” —Expert B
Funding for researchQ39“So, that is really probably what, in the long run, will be the best solution is to have all these experts advocating on behalf of the children with those diseases, and convince the powers above to come out with RFAs for – specifically for childhood SLE conditions.” —Expert S
Q40“I’m seeing more young investigators not able to stick with it…the funding situation has gotten so difficult that it’s really hard for them to stay in the game and they get discouraged.” —Expert R
Mentoring for young investigatorsQ41“And it’s really tough then to, A, find the people to do it who have the time to do it and, B, have the mentors who can teach the next generation to do it and I think that’s a huge problem that we need to address.” —Expert D

  • CARRA, Childhood Arthritis and Rheumatology Research Alliance; cSLE, childhood-onset SLE; FDA, Food and Drug Administration; MMF, Mycophenolate mofetil; PROs, patient-reported outcomes; QI, quality improvement; RFA, request for applications; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; TB, tuberculosis.