Dr. Rachael Grace

I would encourage everybody to ask their hematologist about research and ITP and whether there's a clinical trial that they might be eligible for, for what kind of clinical trials are open in their age group or their type of ITP. I think that it's incredible what's been accomplished already. And I think it's exciting what we're going to see over the next five to 10 years.

Narrator

Welcome to the PDSA podcast, Bruised but Not Broken: Living with ITP. The diagnosis of a bleeding disorder like immune thrombocytopenia may leave you wondering, how can I really live my life with ITP? PDSA's podcast, Bruised but Not Broken: Living with ITP, brings empowering stories, the latest research and treatment updates, lifestyle tips, and answers to the real life questions the ITP community is asking. Here’s your host for this episode, Barbara Pruitt.

Barbara Pruitt

Hi, good afternoon, good morning, wherever you are. Today's topic is really one that you've probably heard about. We're going to go over clinical trials. And if your hematologist has mentioned clinical trials to you, today we're going to get the answers about what they're all about, and we've got an expert on that. Today we have, as our guest, Dr. Rachael Grace. She's a pediatric hematologist, at Boston Children's Hospital. She's an associate professor of pediatrics at Harvard Medical School. And she is the medical director of the hematology clinical research program at Boston Children's Hospital. She enjoys the clinical care of pediatric patients, and her interests are on focusing on improving the outcomes and the care and treatment of individuals that have immune cytopenias. And to top it off, she is also a member of the PDSA Medical Advisory Board. So we want to welcome you today, Dr. Grace. Thank you so much for joining us.

Dr. Rachael Grace

Thank you so much for having me.

Barbara Pruitt

This is a treat because I know personally I’ve been and a couple clinical trials and I still have questions. So, I know that people out there who are, you know, considering a clinical trial or asking questions about it, this will be a great topic for them today. So, when people hear the term clinical trial, they don't really know what it means. So, could you explain that to us? And how is it different from your standard medical care?

Dr. Rachael Grace

Sure. Well, clinical research in general is the study of health and illness in people. And a clinical trial is an example of a type of clinical research. In a clinical trial, a specific test or treatment is being studied to see if the intervention helps to prevent or to treat a condition. And in a clinical trial, volunteers give their permission or their consent to have a treatment to study it's safe or ineffective. An example would be an interventional clinical trial for a drug that's being studied to see if it's safe and effective in ITP. And years of research lead to a clinical trial. So, a lot of data is already known before a drug is ever given to people who have a condition as part of a clinical trial. And strict rules and monitoring are in place for the oversight of clinical research and clinical trials. And it is really important to understand how research is different from standard medical treatments and what's involved in participating in a research study. And I can highlight a few of these differences. So, one difference is in terms of the intent of the of the treatment. So, in medical treatment and routine care, you're addressing the needs of an individual person, and the intent is to treat that individual person. But in clinical research, the intent is really to answer ah research question through volunteers. And the intent really is to help people in the future. The hope is that as as part of the trial that you're helping the person who's in the trial, the volunteer, but the intent is really to benefit future people.

Barbara Pruitt

So, it's not just for that end of individual person, it's for the benefit of the whole ITP community when we're when we're talking specifically about ITP clinical trials.

Dr. Rachael Grace

Community, that's right.

Barbara Pruitt

So, what got you interested in even participating in clinical trials?

Dr. Rachael Grace

So, I had an interest in in clinical research before I ever went to medical school. When I was learning about the different sciences as an undergraduate, it's natural to ask a lot of questions. And it was surprising to me that so many of the questions couldn't be answered. And so, I got involved in research even as an undergraduate. And then when I went to do my pediatrics residency, and then beyond that as a pediatric hematology oncology fellow, I started to meet patients and families affected by ITP. And I was surprised by how so many of the questions that the families had and that I had couldn't be answered in terms of I which patients ITP was likely to self-resolve and when was it going to self-resolve, who was going to have bleeding symptoms in the future, which treatments were going to work for individual patients. And it was getting and involved with these with these families that got me interested in clinical research in ITP and immune cytopenias in particular. And during my fellowship and now you know for years, have been involved in in different forms of clinical research and clinical trials, looking to see and what new medications might be helpful for people with ITP, but also and ah running and being a part of other types of clinical research, observational studies like registries and survey studies that help us to learn a lot about ITP as well.

Barbara Pruitt

Well, that's great. That's a lot of information, and I'm glad you're one of those curious people that really delve into this because those great minds are the ones that are going to form the answers, and the clinical trials are an integral part of that. When you have a patient, and I know yours are pediatric patients, but for also adult patients, at what point would you suggest to them that they might consider a clinical trial?

Dr. Rachael Grace

So, I think, you know, I keep bringing it back to clinical research in addition to clinical trials, but that's partially because I think there's so much to learn even outside of clinical trials. So, in our clinic, as I think in in many academic clinics, parts of hospitals that are part of training institutions and in medical schools, we offer research to every family that comes who has ITP. So that's a part of our routine practice because we hope to have something available for everybody because we think there's opportunity to learn from everybody if they're willing to participate; be good candidates for an intervention, a new a new drug trial. I think you know part of it is people who haven't had success with treatments that they've tried in the past where either they've not tolerated prior treatments or they've not had a good response, a platelet response or bleeding response to prior treatments, especially people who've tried a number of different treatments in the past. Those individuals who still have symptoms and manifestations of ITP where it's affecting their everyday quality of life. Those are people where we would be talking about what's possible in a clinical trial and what open trials might be ones that they should think about. think too there are people who are really interested in helping to further medical knowledge, you know, that are invested in that and want to try something new, even if they've had something that's been effective for them but are interested for a variety of reasons in trying something new. And I think, too, there are things that stand in the way of routine medical care, like the cost of care. So, for some people, unfortunately, they have access to some treatments but not other treatments. And having a clinical trial makes you know potential new drugs accessible to some people where maybe they don't find accessibility to other treatments. It also allows for the cost of that care to be paid for by research. So rather than having to pay for your own care or you're having your insurance or payer coverage cover the care, the cost of the treatment, the cost of the monitoring, the cost of all those visits is paid for by the research. And for some people, that's a major benefit because they don't have the type of coverage that they wish they had for treatment.

Barbara Pruitt

Right. Well, to specify, clinical research is really like answering questionnaires and surveys, registries, and a clinical trial has to do with an intervention.

Dr. Rachael Grace

An intervention.

Barbara Pruitt

Correct.

Dr. Rachael Grace

That's right.

Barbara Pruitt

So that's where the two separate between the research studies and then then the actual medication that they're trying out.

Dr. Rachael Grace

Or the, I would say too, that clinical research is like the big category and clinical trials is a type of clinical research and the surveys and the registries are what are called observation.

Barbara Pruitt

Okay, right, okay, that makes sense.

Dr. Rachael Grace

Also, there's observational studies and interventional studies. The interventional studies tend to be those clinical trials where people are trying a new drug and the observational studies are the surveys or registries. But I think that people sometimes don't realize how important those observational studies are. And a lot of the ways that we practice come from observational studies, you know, in terms of knowing the frequency of bleeding symptoms and what but populations of people with ITP might be observed versus requiring a treatment or even our testing and monitoring approach, you know, which types of tests

should we be sending in people who have ITP and what do we do with the different results. An example of that, if I can share an example, is that the Sarah Vance group in France have really great observational data about people with ITP.

And in their study, when they looked at the time when somebody first came in with an immune low blood cell count, they checked a test called an anti-nuclear antibody, an ANA test. And if that test showed a high positive rate, a significant percentage of young people went on to develop lupus, a more systemic autoimmune problem. And what they saw also in their data is that if people had that high positive test and started on a medicine called hydroxychloroquine, that that significantly reduced the rate that people who had ITP went on to develop lupus. So that was all observational data, recognizing maybe we should be sending this test in certain people, and maybe we should intervene based on the results.

Barbara Pruitt

Wow. Right.

Dr. Rachael Grace

So that was without, you know, without an intervention, all observational. So, it's an association without knowing what causes what. But that association is important to know about. And we can't always do interventional trials around everything because they're expensive and hard to conduct. And so this observational data can be really strong and helpful in terms of keeping people healthy.

Barbara Pruitt

And that collected data is so important, and that's why, like the PDSA has their natural registry for ITP patients, and we really encourage all patients to go online and fill that out as much as they can because that information is so valuable.

Dr. Rachael Grace

Absolutely.

Barbara Pruitt

If you are telling or asking someone to participate in a clinical trial, meaning having an intervention of some sort, what are the concerns and hesitations that you see in your patients or the patient's parents in your case?

Dr. Rachael Grace

I mean, I think people have a lot of reservations sometimes about research. I think one is, you know, people don't want to feel like they're part of an experiment. You know, the people say, oh, I don't want to be a guinea pig or something like that. And I think, you know, talking about, well, what do we know about the type of trial we're talking about? Where does the data come from about why we think this medication might be effective in ITP? And, you know, all we know about the safety and the types of studies that are done before you get to the trial. So, I think having that information is extremely helpful.

Another reservation is around privacy. So, people worry about having their medical information somehow known to a company because a lot of the interventional trials are run, are sponsored and designed by a pharmaceutical companies. They're run oftentimes with a clinical research organization. They're sort of a middleman in the middle, and then and then they're conducted at the hospital with hematologists. So, they're worried about other people having their medical information. And it's important to know that everybody who participates in a study is assigned as a complex study ID, and their information is what we call de-identified. It's not associated with their private information. So that the information is collected, but nobody knows that it's that individual person except for the people who are who are at the site. And that informed consent form, that process of getting permission, volunteering to participate really goes through who has any of your health information and who can see it so that you have all those details so that you can be informed as to, you know, who has any of your private information. And then I think people are, are you know, worried sometimes about the time that it takes to participate in a clinical trial, that it's not the same as routine medical care, that there's, you need to come to specific visits on specific days and have certain tests done, that when you have routine medical care, there's a little bit of a negotiation with your clinician about deciding, well, when do you really need to get blood work done? When do you need to come back for an in-person visit or virtual visit, but with a research study, it's really like following a recipe. You have to do exactly what it says, and that can take time away from work or school or other commitments that you have, and you have to feel invested in taking that time. The flip side of that is you get really, truly excellent care as part of your clinical research, clinical trial participation, that you have a huge team of providers that are looking out for you bigger than part of your routine medical care because you have research nurse and a research coordinator and a hematologist and others who are wanting to know all your symptoms, any medical issues that come up, want to see you regularly, test you regularly, so you have very attentive care while you participate in a clinical trial.

Barbara Pruitt

Well, I have to agree with that because I've participated in a couple of clinical trials, and you're absolutely right. You get such great. medical care because the doctors really focused on you and how you're responding and if you have any side effects. And then the research coordinator in the office is asking you a ton of questions, going over absolutely everything, things you wouldn't even think of. But it's all information that's gathered that really benefits in the long run to see whether this intervention is a good one or and working or not. One thing I think that a patient might be concerned about or a parent of a patient is the cost of a clinical trial. Could you explain how that works? Because I know there's no cost for them to participate, but it does take a lot of energy. It is part of, you know, being the physician that's running it, and then there's additional staff and the clinical coordinator. How is all that expense shared? How does how is that handled?

Dr. Rachael Grace

I think there are lots of different ways of looking at the cost. I mean, I think the way that I try to think about it as let show and is, you, is there's cost for the ah cost for to the to the patient, the participant. And as you were just saying, the cost for the study drug, for the visits, for the monitoring, that's all paid for by the research study. From the patient perspective, there's the cost of missing work or missing school or other commitments. And that cost isn't really taken care of as part of the study. So, I think that we think about the financial impact just in terms of the medical care, and that's paid for. But there is an impact in terms of what you might have to miss in order to participate. And I think everybody who designs a study tries to be really cognizant of that and tries to decrease the impact of that as much as possible. And you are right, though. There's you know a lot that goes on in terms of the on the medical end at the hospital in terms of how do you conduct a study and how do you pay for all of that. And that is a, it's in in and a very complex system. But there are lots of different ways that this gets paid for, depending on the type of study it is. So, if it's a pharmaceutical company that's designed a study and is sponsoring a study, then they'll pay for the costs with a budget at, before the study ever opens to support the research nurse and the coordinator and the team that's needed to conduct the study and to u pay for the lab tests and the room and everything of how the study needs to be conducted.

If it's not with a pharmaceutical company, then then we look to you know government research funding or philanthropic funding or patient group funding to help support studies. And I think, you know, what but questions get asked by pharmaceutical companies are sometimes different than the questions that we want to answer in clinical practice. For example, the clinical trials that are run by pharmaceutical companies often compare a drug to placebo. And the placebo is there because the regulatory agencies want to know about the side effects of the drug versus the side effects we see in somebody who's not getting the drug that might be from the condition. And we want to see too, if there's improvement in people getting the drug compared to the natural improvement, we might see in people who aren't getting the drug, who have the condition. But in real practice, we don't, we're not thinking like, oh, and this individual person, should we give them a medication or should we observe them and not give a medication? Usually we're thinking, should we give somebody this medication or another medication or another medication. We're sort of looking to compare across them. And those kinds of studies have been rare in ITP because they're not the kinds of studies that pharmaceutical companies are interested in. So, I think it's important to have funding from lots of different places so that we can try to answer all the important questions in ITP.

Barbara Pruitt

Well, and it's important for the patient to know that it's not going to be a financial burden on them specifically. And it sounds like they do try to accommodate that the patient as far as missing work or whatever, try to be a bit flexible.

Dr. Rachael Grace

Absolutely.

Barbara Pruitt

I know one of the things that I recall from being in clinical trials is that number one, I've never been pushed into it. It's always been explained from A to Z, every question I had which was answered completely, even if I asked it twice or three times. It is completely voluntary. And you can withdraw at any time if you're feeling uncomfortable. My feeling towards going into it was, hey, listen, nothing's worked so far. Maybe this will be the answer. Maybe this will work for me. But if it doesn't work for me, if it helps the ITP community in some way, I think it's worth it. So, I know that's an kind of an altruistic attitude, but I think the people that are involved and decide to do that have a bit of that with them, don't you think?

Dr. Rachael Grace

I do. I definitely do. And as you're saying, it's exactly right that it's always a choice. And it's important to feel you've had ample opportunity to think about whether you want to participate, to have had the time to talk with other people, other providers, family, friends about participating. You should never feel rushed into a decision about participating and you can always change your mind about income and come off the trial even after you've started on it. So, it's always a choice and that process of being informed about the trial, that consent process, it's an ongoing process. So even, you know, you review it, you review this form, you go through all the information. You might go through it a lot of times and go through all your questions. But even after maybe you've signed it and you're participating and you're on the trial, if some new information comes along, you're going to be updated about that new information. A new and consent form is going to be reviewed with you and you're going to go over that and the new information and the older information will all over again and your permission is going to be asked for again, you want to participate anytime there's new information? So, it's really an ongoing process that happens the whole time that you're on a study. But I agree with you too that it's an altruistic decision because it is something that may benefit you, but really the hope is to benefit people in the future and other people who have ITP.

Barbara Pruitt

Right. And I know for myself, it was not presented in one day that they needed an answer. It was given to me, they gave me information, I could think about it, we talked about it a second time, might have visited, and You know, it was a while before I said, okay, let's go ahead and try. And again, it's nothing that's forced on you, which I think is important to remember. And one of the things that made me feel comfortable was knowing all of the steps that this clinical trial went through before it was at the point where they were giving it to actual patients. And could you explain a little bit about how all these rules and regulations are put in place? to protect the patient.

Dr. Rachael Grace

Sure. I mean, there were lots of ways of thinking about it. One is in terms of the different phases of a clinical trial, even, you know, the data that you need in order to get to a clinical trial, that's actually in people who have a condition. So, there's work that's done in the lab before ever getting to people. That's called preclinical work. And that's done in test tubes, but sometimes done in animal models too, and trying to figure out both whether the drug is effective and if it's safe too. And then sometimes it will move to different phase trial called a phase one trial where a drug is given to healthy people really to look at what the right dose might be in terms of safety. not looking to see if it's effective, but really looking at purely at safety. And after that, then the drug might get to people in a phase two or three trial. And there are lots of steps, as you said, that go into place to make sure that there's oversight and that the drug trial has been designed with rigor. One initial part of that is going through the Institutional Review Board or Ethics Committee at each institution where the study is open. So that's a process of explaining all of the aspects of the protocol and the trial to a committee of people whose job it is to oversee the conduct of research at that institution. And that has to happen at every hospital where that study is open all over the world. Each place has a different process but following the same principles. There are also, as part of drug trials, what's called a data safety and monitoring board or committee. That committee is a group of statisticians and clinicians who meet and review the data separate from the trial. They're not involved in any other way. They're not part of a company. They're not part of the hospitals conducting the study. And they review the data periodically while the trial is being conducted to make sure they're not seeing safety signals of a problem with the study drug. And they ask critical questions of the people conducting the study to make sure everybody's looking at all of the data carefully along the way and that the study is stopped if it's not safe or if there other reasons to stop the study. And then there's regulatory agencies that oversee our trials too, like the FDA in the US, s to make sure that the conduct of the trial is following the important regulations.

Barbara Pruitt

Well, that's great. That should be a relief for a person who's considering it too, that if something, if there's a side effect that's showing up elsewhere and they want to stop the study, you're going to know that because that information is being collected constantly, I'm assuming, correct?

Dr. Rachael Grace

That's right. That's right. Constantly collected and constantly being entered into a ah date ah database that's de-identified, has that number associated with each person, so nobody knows who anybody is. And each site enters the data, and it goes to a central location where they're looking at it periodically to make sure that they're not seeing safety signals. The other thing that happens too as part of trials is if there's a safety event, there's a big report that gets filled out by the site around that safety event, and that report gets disseminated to every other site that's conducting the trial. So, you know in real time about any important safety signals even before anything might get changed with a protocol or the consent form, the person who's leading the study at that hospital site knows about that safety issue.

Barbara Pruitt

One thing I was thinking about as you're speaking is the hospital site. Clinical trials can also be performed at clinics, correct? I mean, or they don't have to be necessarily always at a hospital or a medical school.

Dr. Rachael Grace

Right.

Barbara Pruitt

They're also open to like large hematology practices also.

Dr. Rachael Grace

Yes, yes. Yep, yep, yep. So, it just needs to be a place where they have the all of the components needed in order to run the study. But as long as all those components are there, that's right. There are lots of different kinds of clinic and hospital settings that a clinical trial can be run in.

Barbara Pruitt

Well, and one thing I know that I've heard through the years is it's really important that people of all ages, races, backgrounds participate in research because ITP does not specify who is going to get it So you really need to have a broader base of people, you know, participating in clinical research. How do you hope to overcome that issue?

Dr. Rachael Grace

I think you talk about research with everybody who comes everybody's clinic, you know, that if you have research open at your center, you offer to anybody who's eligible. You have to make sure the research can be, pertains to everybody who is affected by a condition, just as you're saying. So, we try to offer research to everybody who comes to our clinic. I think that's the way to make sure you're getting wide spectrum of people participating is really to offer research to everyone.

Barbara Pruitt

And to answer their questions, to allay their fears, if they have some, you know, fears about it, I think the conversation is so important. What would you say to patients or caregivers that are listening today? Where should they go to learn about clinical trials and whether it might be something that's right for them?

Dr. Rachael Grace

I would encourage everybody to ask their hematologist about research and ITP and whether there's a clinical trial that they might be eligible for, for what kind of clinical trials are open in their age group or their type of ITP. And if there are observational research studies, like was mentioning, registry surveys that they might be eligible for. So, I think starting with your hematologist is a great place. There's also, as you mentioned, through PDSA, some research that's open to everybody. So there's the PDSA Natural History Study Registry that's right on the website. So, people can go to the PDSA website and find it right there. And that's open to everybody who has ITP. That's a great resource for participating in research. There's a more complex site that is comprehensive but difficult to understand. That's called clinicaltrials.gov. And that is a place where all clinical trials need to be listed for everything, including ITP. So, you can search ITP on that website, but it's very challenging to understand the information that's there. But you could definitely look there too to see what clinical trials are open for ITP.

Barbara Pruitt

And is that with the National Institutes of Health, the clinicaltrial.gov? I believe it is. Or I've gone on NIH.gov and I've found information about clinical trials. Maybe it sends me over to the clinicaltrials.gov.

Dr. Rachael Grace

It does. I think it does. That's right.

Barbara Pruitt

Yeah. Okay. That could very well be. And what do you see as far as the end result? What do you hope to see as far as our clinical in ah any clinical trial that you're involved in or that anyone's involved in? What does the end result mean to you?

Dr. Rachael Grace

I mean, I think everything we know about ITP is from clinical research. And it's such an important part of making progress. And it relies on the interest of clinicians, but it really relies on the interests of people who have ITP. And it's that partnership where the most progress is made; see this as a way to better care. I mean, this is where we have to be to make progress. So, if you feel frustrated by unanswered questions or treatments that don't work for you or symptoms you have like fatigue that aren't getting better, with the current therapies and things that you're doing, get involved in research because I think this is how we're going to make progress. And we've seen huge progress. I mean, it's to come, but it's already happened that there are things that we know about ITP in terms of its natural history, in terms of diagnostic tests that we need to do the ones that we don't need to do, types of monitoring that we do need to do and don't need to do. And we have an array of treatments that keeps growing, you know, that that list of possible treatments and treatments that have novel ways that they work, you know, that there are new medicines with new ways they affect your immune system or the way that ITP has evolved for you. So, I think that it's incredible what's been accomplished already. And I think it's exciting what we're going to see over the next five to 10 years.

Barbara Pruitt

I agree. I think so much has been accomplished in the last 20 years with the knowledge and the research, and it's just growing and growing. And I think the future looks very bright with continued research and clinical trials and all this research studies and stuff that they'll all come together and hopefully give our patient population a lot of options in the future and successful options for them to treat their condition. Well, I can't thank you enough for clarifying so much of this for our ITP patients. And I hope that, you know, as they look at our podcasts and we have little blips about what each podcast is about. If they're considering a clinical trial or if their doctor has mentioned it to them, they can turn to this podcast and hopefully a lot of their questions will be answered. So, thank you so much for being here and for answering these questions.

Dr. Rachael Grace

Thank you so much for having me.

Barbara Pruitt

And I wish you lots of luck and lots of lots of work in the future and lots of answers particularly. So thanks again and I hope you have a great day.

Dr. Rachael Grace

Thank you. Thanks for having me.

Narrator

How do you live your life with a bleeding disorder like ITP? From working in the kitchen with knives, to navigating sharp corners in your house, going out to eat in a restaurant, traveling on a plane, attending a sporting event, even dancing at a wedding. ITP patient, Barbara Pruitt, shares her tips and tricks for moving through life with ITP for more than 60 years. Here's her lifestyle lesson for the day.

Barbara Pruitt

Back in 2007 or 2008, I was presented with the opportunity to be in a clinical trial for a new TPO medication. At the time, I was anxious about my low platelet count and the inability to find a successful treatment, so I went ahead and enrolled. I figured I had nothing to lose. If it didn't help me, it might help someone else with ITP. I went into it with great optimism. But unfortunately, it didn't work to elevate my platelet count, so we stopped the treatment. Was I disappointed? Yes, of course. But in a way, realized that my participation in the clinical trial could benefit the ITP community as a whole. After all, the drug was approved and has been in use now for over 15 years with great success. We are all responsible for our own care, but we need to realize that there are ways we can also help others. By participating in a research study, you will be helping our ITP community, whether it's a survey that's been offered to you or if you visit the ITP Natural History Registry on the PDSA website. The information that's gathered is used to further research on ITP. All it takes is a little time, and it's painless. Depending on your location and availability, a clinical trial is another way that you could help. So, in the future, if you are presented with this opportunity, give it some thought. It could be the treatment that you've been waiting for, and you won't know unless you try. So, until next time, I'm wishing you lots of happy, healthy platelets.

Narrator

Thanks for listening to the PDSA podcast, Bruised but Not Broken, Living with ITP. Made possible by our presenting sponsor, Amgen. Special thanks to Gus Mayorga for composing our theme music. To see what's coming up, visit our website at pdsa.org and subscribe wherever you get your podcasts. Please share this podcast through social media with anyone who you think might benefit from the information and stories we share with the ITP and other platelet disorders community. As always, please speak with a healthcare care professional before making any treatment decisions, but know that pdsa.org is a wealth of information and resources to help you navigate life with ITP and other platelet disorders. Remember, you are not alone.