December 4, 2019
Children have historically been excluded from medical research studies and clinical trials in order to protect them. While this exclusion is well intentioned, we need pediatric research to answer important clinical questions and improve clinical care for this patient population. On this episode of Raw Talk, we explored the nuances of pediatric health research and clinical practice. Our conversation started with Dr. Elizabeth Stephenson, Staff Cardiologist, researcher, and Chair of the Research Ethics Board at the Hospital for Sick Children (SickKids), who shares why it's so important to include vulnerable populations, like children, in research and the ethical considerations that make this possible. Dr. Stephenson also discussed concepts including capacity, consent vs assent, and risk vs benefit in the pediatric setting. We also spoke with Nurse Practitioner Tara McKeown and Clinical Research Nurse Andrea Cote about their exciting and challenging roles in the New Agent and Innovative Therapy (NAIT) program, conducting early phase clinical trials at SickKids. Finally, Dr. Paul Nathan, Director of the AfterCare childhood cancer survivorship program at SickKids, shares how clinical care differs in childhood vs adult cancer survivors, the concept of "shared care" in this field, and both he and Dr. Stephenson discuss the importance of including children and adolescents in conversations about their health.
Written by: Melissa Galati
Pediatric Oncology Group of Ontario
All Ontario AfterCare Programs - POGO
SickKids AfterCare Program
New Agent and Innovative Therapy (NAIT) Program
Children's Oncology Group (COG)
Ronald McDonald House Toronto
Dr. Elizabeth Stephenson There are historical differences with regard to protectionism of children. So people were understandably very reluctant to allow children to participate in research. They typically can't consent for themselves, particularly the youngest children. And so for another person, even a parent to accept risk on behalf of a child is a complicated concept. And so that's been an issue and for a long time, it was forbidden to do research on children. The problem with that is it's introduced bias, where we actually don't have good ways to treat children for a lot of diseases because we're explicitly forbidden to test things on them.
Aditi Desai As you may have already guessed, we're diving into medical research in the pediatric setting on today's episode, you just heard from Dr. Elizabeth Stephenson. Among the many hats she wears, she's currently the chair of the research ethics board at the Hospital for Sick Children. So we knew talking to her would be a good place to start. As Dr. Stephenson mentioned, we're very reluctant as a society to allow children to participate in research, and understandably so.
Biren Dave There are many barriers to doing so ethical, legal, clinical, etc. Yet, it is incredibly necessary. We need to involve children in research to optimize their clinical care. Although the demand for pediatric research remains high. The logistical implementation is complex, in large part because we generally perceive children to be vulnerable study subjects. On today's episode, we sit down with four clinicians from the Hospital for Sick Children and dive into the nuances of pediatric research ethics, early phase clinical trials involving children, and the long term implications of disease and this unique and diverse patient population.
Aditi Desai This is Aditi.
Biren Dave I'm Biren.
Frank Telfer And this is Frank.
Aditi Desai Welcome to Episode 70 of Raw Talk.
Biren Dave As we've already mentioned, Dr. Elizabeth Stephenson is the chair of the research ethics board at the Hospital for Sick Children. She's also a staff cardiologist and researcher at the hospital, as well as a professor of pediatrics at the University of Toronto.
Frank Telfer In many areas, pediatric medical research is considered to be somewhat behind adult medical research. What factors do you think have contributed to this? And does the lack of pediatric medical research make evidence based medicine particularly challenging in this population?
Dr. Elizabeth Stephenson In much of pediatric medicine, we're extrapolating from the adult literature, whether it's in observational studies, you know, randomized trials, there's almost never the depth of information in the pediatric world, simply because kids are usually healthy, which is good. And so for a long time, doing drug trials in children was exceedingly difficult. But there is a real awareness of this now. And I think a move towards making sure that we're promoting safe ethical research in all populations, pregnant women is another population that sort of famously underserved by research, because people are terrified as to what the effects might be on the fetus. So I think both of those there's a real move to include those populations in research in a safe way. The solution to vulnerable subjects is to protect them within the research not to exclude them from the research.
Aditi Desai In many ways, it is understandable that we would want to protect children. But we have to strike a careful balance between protection and inclusion in order to ensure that kids can be sure to benefit from the breakthroughs being uncovered through medical research.
Frank Telfer I wanted to ask you about the principle of justice in the context of pediatric research ethics. For justice to be met, individuals within a population must have equitable access to the potential benefits of research or of a given intervention that might be under study. For this to be achieved, they have to share and the potential risks. Would you say that the past exclusion of children from research studies in many areas might be unjust and thus challenging from an ethical standpoint?
Dr. Elizabeth Stephenson It's hard to make a sweeping statement like that because I think that there Are some studies where children would be appropriately excluded and others where they're inappropriately excluded. I think the principle that you mentioned, of justice is exactly the right thing to think about. So are you excluding children, because they are at higher risk from the research and thus they would have an undue burden of risk. And then it might be just to exclude them. But you have to recognize that in and excluding them, you also exclude them from all of the benefits both the knowledge gained and the potential access to the experimental therapies. So I wouldn't want to make a sweeping statement about it, because I think it does very much depend on the research. But certainly, the tendency to not allow things to be tested in children is not just
Frank Telfer Is research generally performed in adults first, then children?
Dr. Elizabeth Stephenson Typically, if there is a biological equivalent of the disease that's being studied. Typically, it will be studied first. in adults, there are certainly circumstances where that's not feasible diseases that manifest differently in children or in their most severe form in children, or your best chance at intervening is at presentation. And so in those circumstances, you may go directly to the pediatric population, to have your best information and your best chance of the research actually benefiting children. One of the things that we know is that diseases that typically express themselves in adulthood, but occasionally present in childhood can be very different in their childhood version. So if I look into my world of cardiac electrophysiology, there's a disease called Brugada syndrome that's caused by abnormalities in the SCN5A gene and the presentation in adults is very different from the presentation that we see in the youngest children. And so although we can learn and extrapolate from both populations, if you look solely at one or the other, you will not get a complete picture of the disease, and ultimately, probably of your therapy.
Frank Telfer More of a general question, what makes a research study ethical?
Dr. Elizabeth Stephenson A general question and an incredibly complicated one, informed consent is essential. And that can be provided by the participants, it could be provided by a substitute decision maker, or, in some circumstances, it can be provided in the form of a waiver of consent, which the REB can provide for a study that's thought to be significantly lower risk to the individual participants. We look for a sense of fairness or justice, we need to be actually scientifically sound. So for example, we would not consider a study that looked at the ability to telepathically influence the people in three countries away and likely to be scientifically sound and so it's a waste of everyone's time, at best, we would consider that not ethical. We look for evidence that is going to be something that is actually feasible and can be carried out when we consider people's budgets, do you have enough money to recruit the patients and do the science that you've said you're going to do? Because if the participants give you their time, energy, saliva, blood samples, whatever it is, and you get halfway down the road, and you run out of money, and it all goes kaput, you know, that is not an ethical research project. Those are the big principles.
Frank Telfer What say does a child generally have in agreeing to participate in research or to undergo a particular medical procedure versus a legal guardian?
Dr. Elizabeth Stephenson It's a great question. It's something that we spend a lot of time thinking about. So whenever a child who doesn't have the capacity to consent for themselves, is asked to participate in research, we do look to obtain assent.
Frank Telfer Just sort of what is capacity, for our listeners?
Dr. Elizabeth Stephenson Yes. So capacity is the ability to understand what you're being asked. So, capacity is very subject dependent. It may be that there are decisions that very young children can make in terms of the capacity. Do you want vanilla ice cream, or do you want chocolate ice cream? Most children have the capacity to make that decision. They know what the ice creams are, they know which one they like better and they know what they're asking for. On the other hand, trying to decide whether or not to participate in a randomized trial of two cardiac interventions, most young children will not have the capacity to understand it's complex. There's a lot of implications both directly in terms of what the experience might be like for the child, but also the potential health risks and benefits. So those are complex things to understand, it's something that we would typically not expect a five year old, seven year old, maybe an 11 year old, the older you get, the more capacity you have in a typically developing child and so with that, the ability to consent for oneself grows with age. We're very lucky in Ontario that we do not have, from a medical perspective, a discrete age of consent. And that means that we can make that decision with the family and with the child on an individual basis. There are lots and lots of 16 year olds who have full capacity to make health decisions. And there are lots and lots of 16 year olds who have no concept of their own mortality, and do not have that. So it's something that we really need to assess for every participant.
Frank Telfer So I guess the say that the child has differs, depending on age and other practitioner to patient consideration. So it's very case by case?
Dr. Elizabeth Stephenson Yeah, absolutely. And I think that there, there are circumstances under which we would not respect a child's assent or dissent. So if the medical research that was going on was also a mechanism to deliver a therapy. So for example, a new medication that is expected to be the best therapy available to the child, just as we wouldn't allow that child clinically, to refuse the medicine, we won't allow them to refuse it within the structure of the research trial, we would, however, still want to respect their dissent for things that were not directly related to their benefit. So for example, if somebody is in this medication trial, where we really do think that this is the best thing for the child, but there's an MRI, that's an optional assessment, and the child is very claustrophobic, we should allow them to dissent and refuse to participate in the MRI even while we're saying no, you need to take your medicine, you need to be part of this, because we think it's the best thing for you. Sometimes that MRI is essential, because it's going to provide you fundamental safety information to protect the child. And then again, it flips back to the category of saying this is in the best interest of the of the child. And we're gonna make it as easy as we possibly can on them, but we're not actually going to allow them to say no.
Biren Dave Now we have an idea of how consent works in the research setting when working with pediatric populations but how does it work in a clinical setting? How do clinicians go about communicating complicated diagnoses and treatments to young patients? We asked Dr. Paul Nathan, a pediatric oncologist at the Hospital for Sick Children. You will hear more from Dr. Nathan and his role as the director of the AfterCare program for childhood cancer survivors later on in this episode.
Dr. Paul Nathan Right. So yeah, I mean, certainly, you are faced sometimes with having complex diagnoses or poor prognosis that you need to discuss with, obviously, with families, but also with kids. And obviously, the sort of developmental age stage and maturity of the kid really influences how you do that. Certainly, when you're dealing with older kids and teenagers, you make an assessment of both their maturity and also their capacity, right, because in Ontario, there's no age of consent. If you can fully understand the disease and its implications and the risks and benefits of therapy, then in Ontario, you're considered to be a competent, I guess, adult for the purposes of making decisions. There's no age of consent. So things like getting surgery or starting chemotherapy if you're 16, but fully cognizant of your disease and the risks of the treatment and the potential benefits of the treatment and the team makes the assessment that you're competent, the decision is actually yours or not your parents. And that may make for a good complete podcast around the ethics around that because there are places where there's an absolute age, you know, it's 18, below 18, your parents make choices above 18, you make choices. But clearly, there's teenagers less than 18, who are more than mature enough and intelligent enough to understand and make decisions. And there's 19 and 20 year olds who may still not be able to a point where they can make those decisions independently. So in the older teenagers, really, we're talking to the teenagers and obviously you as with any cancer patient, you talking to you you always are trying to couch it in language of hope, you know, hopefully, when as a new patient, there is a pathway to cure and the hope is really about how we're going to get you better. Sometimes kids have disease that's not curable and although we often start really trying to find a way to cure them, sometimes this becomes clear that that's not going to happen. And then those hopes sometimes change right to the importance of spending time with family, or the importance of not suffering from serious symptoms and those sorts of things. And we have conversations with these teenagers about these things. But as you can imagine, that's incredibly difficult. We have a whole team, you know, we've got social workers, we've got child life specialists, the whole family is part of that team. In younger kids, it's different, right? Because you can't really explain to a four year old what having cancer means, and they don't get to make decisions, which is often challenging, right? Because, you know, particularly when you're having, you know, nasty things being done to you, injections and procedures and stuff, and you have no control over it, that's very difficult as a toddler, for example. But we certainly try and explain what we're doing so that there's no surprises. So if they get to get a needle, we explain it, and we try and support them through it. But we try and use language that they can understand. I don't think a lot of four, five year olds can understand the idea of cancer and the fear that goes with it, but they can certainly understand being sick, being in hospital, needing different procedures, all of those sorts of things
Frank Telfer is the child's usually included in conversations that occur between researchers and or clinicians and their parents or other legal guardians.
Dr. Elizabeth Stephenson It's highly dependent on what the study is. So just like for clinical informed consent, there are conversations that you may have with the child in the room and there are conversations that you may not have with the child in the room. When I'm discussing with a family possibly doing a cardiac ablation, some of the youngest children would get very frightened if they heard the details of how I access the heart and what I do. But the parents need to know that information. So sometimes the children choose not to be part of that discussion. On the other hand, some children want every single detail and that absolutely should be respected. And I think that is very similar for clinical and for research consent. Obviously, we're not offering clinical procedures unless we've already decided it's in the best interest of the child. So for research that the optional components need to be explored directly with the child particularly carefully in age appropriate language,
Aditi Desai It is clearly a tremendous challenge to determine what information a child has the maturity to fully comprehend and be comfortable with. This challenge must be balanced with the obvious need to ensure that children are given the best opportunity to assent to the research being performed on them. As researchers, we must be cognizant of these challenges as we seek to move pediatric medicine forward.
Frank Telfer On a more practical consideration than if in the large majority of cases we're not performing the early phase trials in in a pediatric setting, how are later dosages determined for drugs, in particular for kids, if we're only testing it in adults?
Dr. Elizabeth Stephenson Absolutely. So historically, that's actually been a huge problem because the big trials have been done in adults, they've gotten their regulatory approvals based on those trials. They've never done the same level of investigations in children with things like pharmacodynamics and pharmacokinetics and so the drugs may never get regulatory approval in the pediatric population. And so then pediatric clinicians are less to guesstimate and say, well, you know, it's half the size of an adult so, let's start with half the dose. We do that clinically all the time.
Frank Telfer As we enter into an age where more research is thankfully being performed directly in the pediatric setting, do there remain certain studies or kinds of studies where we might have to rely more so on adult literature given the challenge, ethical or otherwise, of performing the work in kids directly?
Dr. Elizabeth Stephenson So what we look at when we're evaluating the research studies is really all around the risk benefit ratio. And for any research where there is unlikely to be direct benefit to the child who's involved, then, it's typically considered to be unacceptable for them to be exposed to anything greater than minimal risk. So when we talk about minimal risk, we're typically talking about access to data privacy concerns, sometimes, exposure to behavioral interventions can be minimal risk, although not always. And, for example, blood that's drawn at the same time as a clinical blood draw, so the child isn't experiencing any pain, but the blood sample is obtained. Those are often things that we would consider minimal risk and acceptable for a substitute decision maker to provide consent for and the child should of course, as such, they should agree to participate when it comes to research that's greater than minimal risk and does not offer potential benefit to the child or sometimes there community, then typically, that's not going to be acceptable. Obviously, there may be unusual circumstances where we would allow it but there tends to be an awful lot of conversation before we'd consider something like that.
Frank Telfer So can children not participate in research where there would be no direct benefit then?
Dr. Elizabeth Stephenson So they can, but it needs to be minimal risk to the child. For example, as I spoke of the collection of blood at the same time as a clinical blood draw, that would typically be acceptable, anything using their their health data with adequate privacy protections in place is typically considered minimal risk, secondary use research. So there clinical data being taken and used in another way, it's typically minimal risk, there are a lot of things that we can allow for children without direct benefit. But when you move into the higher risk things, anything that involves an invasive procedure, administration of a medication, anything like that, then typically you need to have at least some potential benefit to the child.
Aditi Desai To determine the risks and potential benefits of new treatment options for children, researchers conduct studies called clinical trials. To learn more about what these types of studies entail, we went to Sickkids to speak with Tara McKeown, a nurse practitioner, and Andrea Cote, a nurse research coordinator, who are both heavily involved in clinical trials run at Sickkids. Tara and Andrea work within the Novel Agents and Innovative Therapy Program, or NAIT for short at Sickkids. NAIT was started in 1997, and has since grown to include many different types of health care professionals, and offer phase one and two clinical trials for children with various types of cancers. The NAIT program is one of a kind in Canada and we asked her and Andrea why such a program is needed,
Andrea Cote You're never going to try something new if you don't do clinical trials. So having new agents and innovative therapies always comes in the form of a clinical trial and being able to offer patients different options, you know, other options that aren't just the chemotherapy options when there are no other available treatments that we know work is so important, I think in the family's journey through cancer. And just in saying that we are always trying to be better, we're always trying to look for the newest and the best for these kids.
Tara McKeown We've been pushed by the families, which is where we should be pushed from they they know when they go into these early phase clinical trials it's not generally speaking, it's not to find a cure, but they want to, they've gone through this and they want to be able to help future families and kids as well, too. And in order for any drug to eventually make its way up into the efficacy models, it would pass a phase three to know if that works and needs to start at phase one. So it's an exciting opportunity to be part of but it's also mostly driven and pushed by families, which is what we focus our careers on as well too.
Biren Dave Clinical trials play an important role in finding new evidence based methods to treat illness. These trials are organized into three phases, in phase one, the safety of the new treatment is determined. Next in phase two, researchers assess how well the treatment works, or in other words, they're testing the efficacy of the treatment. If a particular treatment is found to be both safe and efficacious, then it can be tested on a much larger cohort of patients during phase three trials to more thoroughly understand its effectiveness. If the treatment passes all of these steps that can be approved for widespread use, one question we had is how are clinical trials and children different from those conducted in adults?
Tara McKeown Typically speaking, in historical trials, they started with low dose and increased up to higher dose to find kind of where the toxicity and where would be the most tolerable doses that what they look for. We normally start at normally very small clinical trials, in comparison to the adult world, which you might hear about, there's no first in human studies that are done in kids. All of these drugs have been used on humans so in adults to some capacity prior to them being used in kids. But we do know that kids are not just mini adults, we know that their metabolism is much different so hence the reason to have those phase one trials.
Aditi Desai Pediatric clinical trials also present unique challenges to both patients and their families. Some of these include accessibility, eligibility and consent.
Tara McKeown So I think challenges would be so certainly for early phase clinical trials, distance from the site, because we're one of the few phase one sites across Canada. So certainly distance for families to travel here, if they're interested in early phase clinical trial. And having the children involved depending on their age, more often than not, they're not consenting to treatment, but they need to assent so they still need to agree to go about this treatment. So that can in itself, there could be some disagreements amongst the family or amongst the child as far as exactly what the family wants to do when embarking on this.
Andrea Cote And I think speaking to that, it's the importance of taking the time to really have the conversation and to make sure that everybody's on board with the treatment before you proceed is essential.
Dr. Elizabeth Stephenson I think that the the biggest challenges that are specific to pediatrics would come when parents really want a child to participate in a research trial that may or may not have direct benefit for them, and the child doesn't want to participate. So examples of these would be very early phase one research trial for a child that has lethal disease, the parents desperately hope that this trial might offer some benefit to the child. But realistically, the research is at too early of a stage that that's a true expectation to come out and children maybe don't want to go through it. That quandary is one that we face on occasion, and can be a really challenging conversation, because we do try to provide family centered care and support both the parents and the child through an experience like that. And there are not easy answers to that balance of allowing the parents every bit of hope that you can, while respecting the child's right to dissent.
Biren Dave Another challenge is getting a child enrolled in a trial in the first place, this process isn't as easy as it may seem.
Andrea Cote One of the hardest challenges with this is the eligibility. So there's often very strict criteria to even be eligible for these trials. And the first step of getting on a trial is doing screening tests and sometimes those tests may come back saying you know what, you're ineligible, your echo function isn't as good as we need it to be to join this trial, for example. And so I think one of our challenges is when we give families this hope, or this potential that there's a treatment option, and then when they don't meet the criteria, and they're not able to join the trial that can be very frustrating and disappointing for families.
Aditi Desai Along with eligibility, accessibility is another hurdle. Since SickKids is one of the only health care centers offering early phase pediatric clinical trials, it can be very difficult for families to make it there if they live far away. Imagine for a second that you're a parent living in Northern Ontario, and your child's physician has referred you to a clinical trial in Toronto. In addition to managing your child's illness, you'd have the added burden of uprooting your life, your family's life, and your child's life in order for your child to enroll in the trial.
Tara McKeown What we struggle with what we talk about the most, especially since we're one of the largest phase one pediatric oncology centers in Canada is having equal access across not only within the province, but also across Canada as well, too. As we all know, Ontario is very big, so ensuring that it's equitable for all of our families, that continues to be a challenge. So getting those resources, so families, if they want to come here that we can actually make it feasible, and it's not going to be a financial, social burden on them. So just engaging all of the team players across Canada who worked on within pediatric oncology, along with the parents and families like they are a strong advocate for their for their kids, which is great. So being able to engage them to kind of increase funding, so it's actually economically feasible for them to make it happen to come here,
Biren Dave A family having to relocate across the country to come to Sickkids for a trial can be very difficult for them. Fortunately, as Andrea points out, there are some resources available to assist them through this process.
The Ronald McDonald House is like an amazing organization and a lot of those families end up staying at the Ronald McDonald House during their stay. And they do offer school there for the kids so they can enroll and do school kind of there which is great. And there's programs and meals there. And, you know, we always try to if we get, you know, tickets to something or anything comes up to kind of offer it to make the experience a little bit better. But it certainly is a challenge for those families that are traveling to be away from their support systems, even extended family who might be helping with some of the care or just emotional support. If you're from a small town, being in the big city of Toronto can be overwhelming, and just navigating the subway, as much as it's part of our daily life here, sometimes not for other people and it can be really hard for them.
Aditi Desai The challenges don't stop once the child and their family get to Toronto to begin the clinical trial. Depending on the child's specific medical needs, timelines can be tight.
Tara McKeown They're often stuck on quite timelines. And never mind the fact depending on their recurrence with their disease, it could be credit aggressive that we actually need to make this happen in a matter of days from time to time. Other times we have more time depending if they've just had surgery, if they just had radiation. But all of the coordination and liaison especially when it comes from an out of center hospital is so crucial and Andrea spends timeless hours just communicating with the outside teams because of course we want all children in Canada to be able to have equal access to these drugs if the families choose to want to but it can be tricky sometimes.
Andrea Cote And it often is like you just drop whatever you're doing and you have to just focus on that and get the kid here as fast as possible, and we're happy if we have two weeks to do all that, but sometimes it is like a matter of days or a week that we have to do all of that stuff and then start the drug. So it can often be quite an adrenaline rush of an experience.
Biren Dave Healthcare is entering an era of precision medicine, where new technologies like genomic sequencing are providing doctors and nurses with new insights on how to best treat certain conditions. How will clinical trials, particularly those in pediatric oncology, adapt to this new era?
Tara McKeown The trials are more so being enrolled based on the biology of the tumor as opposed to the specific tumor itself, there is still trials out there that are looking at disease specific for sure. But more often, now we're seeing that they're actually looking within the biology of the tumor. So it might be a really rare one-off pediatric cancer, but they might have this mutation within their tumor that is common across another group of cancers. I think we need to remember that pediatric cancers are all rare in general, there are some rare entities within there. But I think with this biological era of medicine, and targeted therapies, immunotherapy checkpoint and out all this exciting stuff, it's perhaps made it maybe not easy as the right word, but more inclusive for all types of tumors because we're looking actually at the biology of the tumor. It's not to say that we're going to have a drug that's going to fix or like target all of these tumors and cancers, but we're better than we were probably a decade or so ago.
Aditi Desai Although the molecular profiling of cancers may be helpful. There's still roadblocks when it comes to treating individual patients in a targeted manner.
Tara McKeown In the area that I work in, in neuro-oncology, there isn't the numbers as there is with leukemia, let's say where is the most common pediatric tumor. So it's taking us a little bit longer to look at that. But the Leukemia world is now really looking specifically at all of the cytogenetics of every leukemia patient in order to be able to determine which kids are going to do really well. And can we get them less treatment because of that? And which ones, which ones do we have trouble treating and why is that so, there's certain markers that they can know up front, and in order to give them more therapy up front. And in brain tumors in some groups, we're starting to be able to do that as well, too. Because of numbers, we don't have as many clinical trials to be able to evaluate if that's happening. But we're starting to get there, we still have a long way to come. The trouble being is when in the case that we do a whole genetic sequence of a tumor. More often than not, we won't have a drug that's going to target a specific mutation. And even if we do, getting access to it is not always available. And even if we get access, we don't know if it's necessarily going to work.
Biren Dave Tara and Andrea highlighted some of the challenges that come with running clinical trials for pediatric populations. To overcome some of these challenges, the NAIT program was started. However, clinical trials aren't the only area in which we need specialized forms of care when working with pediatric populations. Specialized care is also required for children who have completed their cancer treatment and are now survivors of childhood cancer. In order to care for the unique needs of childhood cancer survivors, the Pediatric Oncology Group of Ontario or POGO initiated the AfterCare program. We bring it back to Dr. Nathan, who is the director of this program at Sickkids.
Dr. Paul Nathan So the AfterCare program was actually started by POGO, which is the Pediatric Oncology Group of Ontario. And POGO brings together the five provincial pediatric cancer center, so Sickkids in Toronto, and then London and Hamilton, and Kingston and Ottawa. And so, docs at POGO had noticed that as childhood cancer survival went up, and in the sort of 70s, into the 80s, there was this huge improvement in survival. There was a time, you know, five decades ago when most kids diagnosed with cancer died. And then over the subsequent decades, because of improvements in treatments, better supportive care, so we could deal with the toxicities of treatments, more and more kids became long term survivors. And so it became clear to the folks who were running POGO that we need to have some plan, what do you do once the treatment is done, but you know that a majority of these survivors will be loving with some or maybe several consequences of a treatment. So they built starting in the late 90s this network of survivor clinics.
Aditi Desai As you just mentioned, approximately 80% of pediatric cancer patients are becoming long term survivors. But care comes at the cost of inferior long term physical and mental health. So I wanted to ask you specifically about the long term effects or late effects of childhood cancer. What are some examples of late effects and specifically, what are some of the psychosocial implications of childhood cancer?
Dr. Paul Nathan So late effects are any long term consequences that are results of your cancer treatment, sometimes they can come from the cancer itself. So for example, if you had a brain tumor that damaged surrounding brain or a bone tumor that caused damage to bone that couldn't be repaired, but most commonly when we think about it, it's the long term toxicities of the treatments we use. So the toxicity of chemotherapy or radiation or bone marrow transplantation that turned into to chronic health problems, many of these are physical. So the most common physical late effects we see are things like heart problems, developing new cancers, for example, as a result of radiation therapy that can cause cancers to grow but really any organ system can be involved. So we see kidney problems, lung problems, liver problems, these problems tend to be pretty specific to the kinds of treatments you had. So no two cancer survivors will get the exact same late effects if they get them, because they may have had slightly different treatments. There are also psychosocial impacts. So the experience of having cancer can impact things like schooling, sometimes some of our treatments can affect the ability to learn. So certainly when we use radiation to treat brain tumors, or some leukemias, it can have an impact on learning, that impact on learning can lead to school difficulties, or can impact you later on in life in terms of job potential, even relationships and marriage and those sorts of things. And then obviously, the trauma of the cancer. And perhaps the challenge with dealing with the physical side effects of therapy can have mental health effects as well. So we know that some survivors are at higher risk for issues like anxiety or depression, or post traumatic stress, different survivors are going to have different outcome, some will do great with very few problems, and some really struggle with late effects with their therapy.
Aditi Desai Okay, so in terms of all these late effects, do you know how they differ from adult cancer survivors?
Dr. Paul Nathan So there are differences, some of the differences are a consequence of the fact that we're treating these kids at a really young age, when many of their organ systems are still developing or growing. And as a result, a lot of survivors of childhood cancer are like more susceptible to treatments that can damage organ function. So for example, the risks for developing heart problems or kidney problems may be higher in particularly children treated at a really young age, where you're at a time when they should still be growing and developing their organs but you've now sort of added these chemotherapy or radiation treatments that sort of damage that ability. So I think one of the things we see is that some of these late effects in children can be more significant or severe than they are in adults. And cancers are different between children and adults. Treatments are different so, some of the things that we see are just a consequence of the types of cancers. So for example, in women who have breast cancer therapy, they may have something called lymphedema, which is sort of swelling of the limbs as a result of the surgery and loss of lymph node drainage. It's not something we see commonly in kids. But for the most part, both children and adults can get late effects of therapy, there's huge overlap between the two. I think one of the things that's really important to remember in kids is if you cure a child of cancer when they're five or 10, for example, they hopefully have decades of life ahead of them, so that if they develop some serious side effect of therapy, their life will be impacted by that side effect of therapy for decades afterwards, whereas adults, particularly those treated later on in life, may not have that many life years left after their cancer. And so sort of the long term impact of some of these side effects, at least in terms of how long someone needs to live with them can be really, really different between children and adults.
Aditi Desai The structure of the AfterCare program is multidisciplinary. You can think of it like a one stop shop for the healthcare needs of childhood cancer survivors. Many different types of health care professionals comprise the AfterCare team, including pediatric oncologists, nurse practitioners, clinical and neuro psychologists and endocrinologists. The team aims to address as many needs of the patients as possible during their visit without overburdening them with appointments. In addition to addressing and managing late effects of cancer, the program aims to take a preventative approach to health care by providing appropriate surveillance and lifestyle counseling to patients. But as many of the childhood cancer patients make it to adulthood, we wanted to ask Dr. Nathan, whether the transition from pediatric to adult survivorship care is a smooth one, do they tend to lose patience along the way?
Dr. Paul Nathan So unfortunately, we do. So you know, when kids are kids, their parents are the ones who bring them certainly for their initial cancer therapy and then usually for the follow up and the truth of the matter is most parents are going to be really vigilant to make sure that their kid or teenager is coming for the yearly appointment. So at least in the pediatric years, almost every kid whose sense the survivor program shows up what happens at the time of transition when they now reach 18 and get transferred into the adult program. Several things one, the survivor has become far more responsible for their own health care. Their parents are starting to sort of play less of a role and suddenly they can't pick them up by their ear and drag them in. They may try but they can't force them to go. Often ,life intervenes, you know, they go off to university they get a job, they get married and have kids. And obviously, all of these things are competing pressures. You know, when you've got a kid newly diagnosed with cancer, you would drive to the ends of the earth to make sure they get care. But now you're 20 years old or, 25 years from that initial cancer, you feel entirely well. In many cases, you know, particularly if you were treated when you were really young, you may not remember much of your cancer. And so this idea of going to one of these five senses, which are often quite far, given sort of the geographic distribution of where people live in Ontario, that becomes a hassle. And unfortunately, for a lot of survivors, they don't come. So we've looked at attendance in the adult clinics, and maybe only about 40 to 45% of eligible survivors go even once. And when we track them over time, a lot of them drop out over time. And so one of the realizations that we have had in progress head of the last several years, is that this one size fits all, if we build a survivor clinic, everyone's going to show up model does not work. Certainly there are people who will continue to come to these clinics, you know, particularly those that have significant long term side effects with a therapy who perhaps feel that they can only get the kind of complex care they need. In a specialized program, maybe those that live closer, we've certainly found when we looked at who comes the further you live, the less likely you were to come. But for those patients live further away, or for those patients who at the moment feel quite healthy, this idea of coming downtown to a cancer center like Princess Margaret, maybe spending half a day, you know, getting there and waiting to be seen for a lot of them, that doesn't make sense. One of the challenges we have is that a lot of these late toxicities are not the kinds of things that appear right away. So you can have your cancer therapy and for years, even decades, you may be totally fine. But then sometime it's in your 30s or 40s, you start to develop heart problems because of the chemotherapy you got, or a new cancer comes up because you've got radiation for your original cancer. And so even feeling well doesn't necessarily mean that nothing's going to happen over time. And so there are lost opportunities if these patients aren't coming back to the specialized clinics. So what we've really started to do the last little while is think can we build sort of a parallel model of primary care docs in the communities who are closer to where these patients live, who would be willing to take on survivors. And so there's actually an initiative now, where we're reaching out to Family Health teams, or academic family medicine residency programs, to ask if they would be willing to take on adult survivors in the hopes that they'll build some critical mass. And that would make it worth their while to actually learn about these patients. Because one of the challenges with family docs are childhood cancer survivors are still really rare, fortunately, because cancer is rare in kids. And so most family docs maybe have one or two at most childhood cancer survivors in their practice, that doesn't give them much time to learn about their specific issues. And if you've got a brain tumor surviving the kidney tumor survivor, their long term problems can be entirely different. And if you're a family doc who's got diabetes, and dementia and heart failure, and all these adult problems in your clinic, when are you going to take the time to learn about these specific survivors and their issues. And so trying to identify some family health teams who've said this and will take on 10 or 20 survivors, it makes it worth our while to develop an expertise. And importantly, they know that the specialized clinics are there if they need help. So if they've got a patient and they worried, oh, you know, we found a new lump or a bump or we're not sure what's going on, we're all just a phone call away. So this model is called shared care, and so there's this push towards this shared care approach, as opposed to this one size fits all in the teaching hospital academic centers, which we don't think works.
Aditi Desai Dr. Nathan just discussed how the shared care approach benefits survivors who may have lost touch with specialized survivorship care programs. We also asked him how the transition works for pediatric patients who are continuously receiving AfterCare and then need to be transferred to adult aftercare at Princess Margaret Hospital.
Dr. Paul Nathan Eventually, everyone needs to be transferred. Now in Toronto, you'll just be transferred to the Princess Margaret program. And we actually have a nurse practitioner who works in both the pediatric side and the adult side. So there's, at least this concept, there's this link, there's this continuity. And over the last five years or so we've also built in a transition program. So once a quarter, so every three months, we have a special clinic where everyone who's 17/18 coming for the last visit at the pediatric hospital who we know needs to go to the adult hospital, they come with their parents for a full day. The morning is sessions, where they're introduced the importance of survivorship, they actually get a tour of Princess Margaret so they know who the people are and what to expect. And then they're given what's called a survivor care plan, which is a document that basically says, this is the cancer you had, these are the treatments you've got. These are your long term risks, and these are the things you need to do to keep an eye on your health, like if you had chest radiation, start getting mammograms and MRI exams at a younger age than you would in the general population. So they're all given this right now, it's paper but ultimately, it'll be an electronic thing. That way, the hope is that if they don't show up at the adult clinic, but go see a family doc, somewhere in the community, they've got a document that says, hey, this is what I need. Because a lot of those family doc will not know. And so it's sort of our biggest job at this transition time point is to empower survivors to sort of take on responsibility for their own health and health care, because at the end of the day, the patient is the only one who can absolutely make sure they get what they need. And of course, you know, some do it really well, and others struggle, and it's how you help the ones that struggle that we struggle with.
Biren Dave Earlier in the episode, we talked about incorporating children into the conversation about their health. However, Dr. Nathan mentioned, some interesting cases, where teenagers entering the AfterCare program, we're not aware that they had had cancer as children.
Dr. Paul Nathan One of the interesting challenges that we actually have is, occasionally we'll have a teenager show up in our survivor clinic who doesn't know that they've had cancer, they will little when they had the cancer, so no one told them, or if someone told them, they didn't really understand what it means. And then for a variety of reasons, as they get older, either the parents, you know, decide, I don't want to tell them because I'm protecting them from this, or the parents are, this was so traumatic for me, as a parent, I can't possibly relive this by discussing it with my child. So often, it just never gets discussed and it becomes you know, when you were little you were in hospital, or when you were little, you had this little lump or bump. The problem is when they get to the survivor clinic, we make it very clear that they have to know because you can't teach someone to be their own advocates if they don't know they their health story. So then that cancer, how they ever as an adult can walk into a doctor's office and say, listen, when I was young, I had leukemia, these were the treatments I got. But sometimes there's actually a struggle with the parents to convince them that telling their kids is the right thing. And you know, it always fascinates us, because on the entrance to the clinic, it says The Sears Cancer Clinic, it's very clear what this place is. And I think we often wonder if these kids actually really know. And the reason they don't say it is because they're protecting their parents. So actually, right now, we're working with a group in the Department of Family Medicine, at Woman's College Hospital, creating a book, how to tell your child that they had cancer. So we're gonna interview with their help about 20 families who chose not to tell their child at the time they came into our clinic to understand sort of the varying reasons why that happened, sometimes it's a cultural thing. You know, in some cultures, cancer is a taboo, you know, and we've had some common, but we've had some patients with a family has not told their relatives that they have a child with cancer, because cancer is considered, you know, such a bad thing that there's almost a shame around it. And I think we even had a kid or to die without the extended family knowing what it was that they had died of, which is really disturbing and distressing. Anyway, so the booklet will, will try and both give rationales to why it's important to tell the kid but then also strategies as to how to do it. Because for parents, that's often a lot of reliving the trauma that was incredibly difficult the first time. So hopefully, that will be a useful tool.
Aditi Desai So one important aspect of your job is to advocate for the needs of the patient, or provide the patients and their family members with tools and information they need to advocate for themselves. And your hope is that the patients and the families will act on your clinical recommendations, but do you sometimes have parents that do not necessarily agree with your clinical recommendation for treatment?
Dr. Paul Nathan It's incredibly hard. Sometimes it's for religious reasons, so the example used most often are Jehovah's witnesses who don't allow blood transfusions and that can be incredibly challenging, particularly in kids on therapies that push down their blood counts that potentially make them at risk without transfusions. And so the hospital actually has developed a whole policy and have actually worked with Jehovah's Witnesses to come up with a policy but there are certain circumstances in which if it was felt, that without blood transfusions, that kid would be at life threatening risk, there's a mechanism for the hospital taking over medical decision making around those sorts of things. So rarely, they can take the they can take that decision away from the parents. You know, there's other places where parents disagree, and you clearly feel like their disagreement is putting their child at significant risk and really, I think the only times that that would happen is when there's a treatment for a disease where the likelihood of cure is great. So for example, standard risk leukemia right now, the cures are more than 90%. If a parent of a young child, were to say, I don't agree with this therapy, it's toxic, you know, it's going to do harm etc. I want to go off to place XYZ for experimental treatment, whatever it is. There have been cases where the courts have had to get involved and at least the medical custody of that child is given over to like children's aid to make those sorts of decisions. Where it gets a lot greyer, I think is twofold, one, if that kid is older, so if the kid is a teenager who does understand the implications of not getting the therapy, but clearly is still under the sway of their parents, that can be a really difficult situation, it's not common, but it happens. And then I think the other place is if you've got a younger child who can't make decisions, but where the outcome is not guaranteed, so a disease where maybe the survival is 50% but the treatments are intensive with long term side effects. And the parents says I don't want that. Those are ones that everyone needs to wrestle with, right? Because to force legally a family to put their kid through treatment that has a high likelihood of not working and if it does work will have significant long term side effects, it's not so clear. So those you know, would sit down as a group would involve the ethics team and legal team. But there's times when we just, you know, we acquiesce to the parents decision, and hope things turn out okay. They don't always, but those can be hard situations, we deal with him on a case by case basis, I don't think you can have sort of a blanket every single time will will do this. But is it hard when we recommend what we think is the best thing and parents choose otherwise? Yeah, it is and it certainly happens.
Aditi Desai Yeah, that is quite unfortunate, and a difficult thing to deal with for sure. But I'm just wondering, on the other end, I'm sure you have families that put a lot of trust and faith in you. But when a treatment plan doesn't work out the way that you had hoped, how do you maintain that sense of trust with the family?
Dr. Paul Nathan Yeah, you know, obviously, that can be challenging, particularly, I think, in a field like oncology, where unfortunately, things, you know, go wrong quite frequently. I think a lot of how you get through it has to do with the relationship you build with the families, sort of the openness and honesty, you try and introduce into a relationship from day one. You know, every cancer treatment starts with what we call a disclosure, which is, you know, once we know the diagnosis tumor x, or cancer y, we sit down with the family, usually for an hour, an hour and a half and we run through everything we explain the disease, what we know about it, we explain the treatment, we spend a lot of time talking about the potential risks and side effects so that they're fully aware there's no totally benign cancer treatments, all of them come with significant risk. And so as much as we hope that these bad things won't happen, we try and be sort of upfront and honest about it at the time they start therapy, and I often apologize to families, I say, this is a lot for you to listen to. But I'm not going to have your child start on this chemotherapy until you fully understand, you know what the risks are. So that if one of those bad things happens, you know, because you've discussed it before, and because it's anticipated, often they'll obviously be upset but it doesn't generally damage the trust that you've built, because it's a thing that you had sort of, you know, explained ahead of time, and they knew it was possible. They hoped it wouldn't happen, but you know, where it's difficult is if something happens, that's totally out of the blue that you never discussed or mentioned. And then it can impact trust, right? Why didn't you tell me this? If I'd known this was the potential toxicity, I would have never said, yes. That doesn't happen all that often. You know, one of the challenges we face sometimes, you know, your child gets cancer, who do you have to be angry at? Right? There's, there's no reason for it. You know, maybe if you spend your life smoking and drinking, and then later on in life, you do develop lung cancer, or something else that's really associated with that lifestyle. You can be upset and angry. But you also know that some of those lifestyle, be it choices or habits that just you couldn't break over the years accounted for it. But when your five year old gets leukemia, there's no one to blame, we don't understand why it happens but it's almost never something that the parents did or didn't do. And I will say, I start off my disclosure talks with parents to say the one thing I want you to know, is, there's nothing you did or didn't do either now, or when your kid was younger, even when your kid was stalled, you know, in the womb, that caused them to get this. We don't fully understand why kids get cancer, but choices are not a big part of it. So, you know, to feel to feel guilty about it is something that they really shouldn't do. Right. But it's, it's really, really hard.
Aditi Desai Yeah, and the families probably appreciate the reassurance that you give them.
Dr. Paul Nathan Right. But what happens sometimes sorry to finish off what I started is because there's really no one to blame, sometimes, not commonly, but sometimes the anger actually gets reflected back at us, because we are the face of oncology, right and so sometimes you need to let yourself within reason, be the person or the team to whom parents can direct their anger. Because short of screaming at the heavens, which, you know, doesn't always get a reply, there's no way to, to channel that, you know, extreme anger and sadness. And so sometimes that gets channeled at us. And, and so we've had some patients that have been difficult because we're parents, because they take out that anger on us. And you know, it's figuring out how much how much do you accept because it's part of their therapy? And where do you draw the line? Because clearly, some behavior is inappropriate, you know, you can't. So, it happens occasionally, it's difficult.
Biren Dave Working in frontline, pediatric care can be mentally and emotionally challenging. Doctors and nurses dedicate their careers to helping children and their families through very taxing experiences on a daily basis, despite the difficult nature of their professions. The clinicians we spoke to are hopeful for the future of pediatric healthcare. We asked Tara and Andrea what keeps them motivated in their work to advance pediatric care.
Andrea Cote I think my favorite part is being surprised. I think, you know, we often are like, we don't know if this will work. And when you don't know you kind of assume that it won't. But then sometimes it does. And it is so exciting. And you feel like you're, you know, you're breaking ground for the next thing and being part of that is pretty amazing.
Tara McKeown And I think for myself is just being part of the family's journey. And whether this ends up being a really positive experience for the families journey as far as their child's tumor or cancer responds, or if it doesn't, but most of the families are especially going on early phase trials, they know that this is likely not going to help their child but they still feel privileged to be a part of something like that, I feel privileged to have been a part of their child and family's journey. And I think we all kind of learned something through that and and helps them have some hope and also perhaps sometimes some closure to a challenging journey that they might have experienced,
Aditi Desai Despite the complex nature of pediatric research and pediatric specific programs. What we heard from our guests, and what we hope you heard as well is a message of hope, hope for the patients, hope for the families and hope for future generations of children who will ultimately benefit from this work. To echo Dr. Stephenson, the solution to vulnerable subjects is to protect them within the research, not to exclude them from the research.
Biren Dave We'd like to thank our wonderful guests Dr. Elizabeth Stephenson, Nurse Practitioner Tara McKeown, Clinical Research Nurse Andrea Cote and Dr. Paul Nathan for taking the time to speak with us and share their knowledge and experiences. And of course, thank you for listening!
Aditi Desai Your hosts and interviewers for this episode were Biren Dave, Frank Telfer and myself Aditi Desai. Content development by Anton Rogachov. Photography by Changmo Kim, audio engineering was done by Ekaterina An and our executive producer was the lovely Melissa Galati.