Clinical Trials: What They Are and Who Should Participate

Clinical trials test whether new drugs or therapies can improve outcomes for patients. Learn how trials are conducted, questions to ask your medical team about a trial, and your rights if you choose to enroll in a clinical trial.

Clinical Trials, What They Are and Who Should Participate

November 15, 2017

Presenter: Dr. Marcie Riches, Associate professor of Medicine, Director of Clinical Research and Data Quality in BMT and the Clinical Medical Director for the BMT clinic at the University of North Carolina Hospitals.

Presentation is 52 minutes long with 28 minutes of Q & A.

Summary: Clinical trials for stem cell and bone marrow transplant patients are an important tool for identifying new and more effective treatments for many diseases. This presentation describes the design and conduct of such trials and what patients need to know to make a truly informed decision about whether to join a trial.


  • The purpose of a prospective clinical trial is to test the effect and the value of a particular intervention in improving patient's outcomes.
  • Before joining a clinical trial, patients meet with the medical team and are given a consent form to sign that details the rationale for the trial, steps involved and time commitment required, and their right to withdraw from the trial without losing access to quality medical care.
  • There are three types of clinical trials: Phase 1, Phase 2 and Phase 3.  In Phase 3 trials, patients are randomized to receive either the current standard of care or the new intervention being studied.

Key Points:

(00:06:54): The goal of interventional clinical trials is to improve transplant outcomes through a scientific rationale.

(00:11:26): Phase one trials are early investigations that measure efficacy (does it help?) and safety (does it harm?).

(00:13:24): Phase two trials evaluate the feasibility, acceptability, and affordability of the intervention for the broader patient population.

(00:16:20): Phase three trials are randomized comparisons of an intervention group and a control group. 

(00:17:57): Randomized or blinded trials reduce unconscious bias that can skew outcomes.

(00:30:19): Highly successful trials may be terminated early so all patients can receive the newly successful intervention.

(00:33:16): Patients should clearly understand the purpose and primary and secondary goals of a trial.

(00:34:56): Patients also should understand the different treatments and obligations (like the number of clinic visits) in each arm of a trial. 

(00:37:26): Payment for clinical trials is complicated and may not always be covered by insurance.

(00:38:38): Patients are also entitled to know the length of a trial, what happens if it closes, and who to contact for ongoing information about the trial.

Transcript of Presentation:

(00:00:01): [Susan Stewart]:   Introduction. Good evening and welcome to the webinar, Clinical Trials, What They Are and Who Should Participate. My name is Sue Stewart and I will be your host for the evening.

(00:01:10): it's my pleasure to welcome tonight's speaker, Dr. Marcie Riches. Dr. Riches is an associate professor of Medicine, Director of Clinical Research and Data Quality in BMT and the Clinical Medical Director for the BMT clinic at the University of North Carolina Hospitals. She serves as a scientific director for the Center for International Blood & Marrow Transplant Research or CIBMTR, under their infection and immune reconstitution committee. And she's also an associated editor for the medical journal Bone Marrow Transplantation as well as a protocol officer and medical monitor for the National Heart Lung and Blood Institute, National Cancer Institute, Blood & Marrow Transplant Clinical Trials Network. Educating patients about the importance of clinical trials is a mission near and dear to Dr. Riches' heart and we're honored to have her as a speaker this evening. Welcome, Dr. Riches.

(00:02:11): [Dr. Marcie Riches]:  Overview of Talk. Thank you so much Sue. It's a pleasure to be able to be here and provide information for patients and their families and talk about this topic, which is important. Clinical Trials are something that are frequently done for all types of cancer patients and we're going to focus a little bit more on how this works for patients going through transplants specifically.

(00:02:40): So, just as an overview, I'm going to provide some information about what is an observational trial versus an interventional trial. We'll talk a little bit about the purpose of clinical trials and the phases of clinical trials as well as the specific purpose within each phase of a clinical trial. But most importantly what I wanted to provide is a list of questions that are important for you to talk to your provider about when you're hearing about a clinical trial and give you some information about how to investigate into clinical trials or participate in clinical trials if this may be right for you.

(00:03:25): Observational trials follow patient outcomes without novel interventions. So, clinical trials are something that we truly think about as looking at and collecting information to try and improve outcomes for patients. Observational trials generally aren't considered truly clinical trials. What it often is, instead, is a means for physicians to treat a patient as the physician deems appropriate, in discussion with the patient of course, but also allows for collection of information for future study. Sue mentioned that I am a scientific director for the CIBMTR. The CIBMTR is an international registry that collects information on transplant patients and performs these observational studies to investigate different ways of improving transplant as well as looking at how transplant outcomes occur and changes that we've seen in the field over the years.

(00:04:31): Prospective clinical trials involve a novel intervention and are conducted in multiple phases. This talk is going to focus much more on prospective trials. And prospective trials means that we are performing an intervention. We have identified something that may benefit our patients and want to try and investigate that in a more scientific manner. In prospective clinical trials have three phases which are considered phase one, phase two and phase three. There are some phase four clinical trials, but those generally are for specific drugs that have gotten a brand-new FDA approval and we may be doing something that's called a post-marketing or phase four trial. That is much more of an observational trial than these prospective interventional trials.

(00:05:22): So, we're going to focus on prospective interventional trials. So, as I mentioned, the whole purpose of a clinical trial is to test the effect and the value of a particular intervention. If we could transplant everyone without complication, without risk of relapse, then we wouldn't have a need for further clinical trials. But unfortunately, we still have many aspects of transplant that we are continuing to try and improve for our patient's outcomes.

(00:06:01): The key issue with a clinical trial is, as I said, it's an intervention. So, in transplant it could be something like using a new stem cell source. We're using a different type of donor such as a haploidentical donor. We could be looking at new ways to try and prevent graft-versus-host disease or GVHD. We could be looking at a new cocktail of medications for the conditioning regimen or preparative regimen prior to transplant.

(00:06:35): Clinical trial interventions are measured and compared to something else. But the other aspect of this is that the outcome of the intervention is being measured and in most instances, particularly in phase two and the phase three portion of trials, it's being compared to something else.

(00:06:54): The goal of interventional clinical trials is to improve transplant outcomes through a scientific rationale. So, as I mentioned, the goal of these interventional trials is truly to improve transplant outcomes and most importantly, that I like to stress to my patients, is that there is some sort of scientific rationale that has led to this trial being designed and being implemented and open so that we can proceed to learn something. It may be an observation that occurred in a basic science lab, and those are often going to be the next step from a scientific basic science lab to a phase one trial.

(00:07:32): It could be looking at something that there's already been some clinical observations. We've already done the phase one trial or one a clinician was thinking outside the box, understanding the basic science and said, "I don't have another good option for my patient. I'm going to try this drug for the management of their graft-versus-host disease."

(00:07:56): It could be a new drug that's already been approved but may be now used in a transplant patient for a scientific reason or even, in some cases, a potential side effect of a drug. There was a pharmaceutical compound that had been previously looked at to try and treat HIV, the virus that causes AIDS, but one of the side effects of that was that it decreased complications that showed that it could potentially be used to prevent graft-versus-host disease and that's gone through and just completed a phase two clinical trial to look at that information.

(00:08:46): Trials ask one specific scientific question but evaluate it with multiple endpoints. Again, there's a primary question for a clinical trial. We always have one specific scientific question that we are trying to answer when we're performing these clinical trials. But there are often multiple other secondary endpoints, and for transplant studies, these are generally based upon the typical events that we see in our transplant patients.

(00:09:14):  So, for example, if we are looking at a trial of a new conditioning regimen, a new cocktail of drugs to prepare the patient for transplant, we will have secondary endpoints looking at things like how long it takes for the patient's blood counts to recover, or what we call the time to engraftment. It may be looking at frequency of graft-versus-host disease or infection complications. That's not the primary purpose of the study, but it may subsequently provide information for future clinical trials.

(00:09:52): Trial endpoints include relapse, survival and progression. I mentioned a couple of different transplant trial endpoint examples. Realistically for our patients, relapse, survival and progression or relapse-free survival are key endpoints in most of our transplant clinical trials and depending upon what is specifically being studied will guide what that primary question that's going to be answered for the trial.

(00:10:23): Graft-versus-host-disease and new toxicities may be secondary endpoints in a clinical trial. The transplant community has made something that we call some composite endpoints, like something we have labeled GRFS which stands for GVHD and relapse -free survival because we know, particularly for our allogeneic transplant patients, we may ultimately trade one disease for another. You may be transplanted for an acute leukemia but subsequently develop graft-versus-host disease that may not be responding as well to therapy. And so, this may become a study endpoint in a new trial. Additional transplant toxicities such as infection or lung damage or heart damage or kidney outcomes may also be secondary endpoints of a trial.

(00:11:26): Phase one trials are early investigations that measure efficacy (does it help?) and safety (does it harm?). There are multiple phases of prospective interventional clinic trials. The first one is called a phase one trial and it's important when you're talking to your physician that you talk about what phase of a trial something is because that will ultimately impact the primary goal of the trial. Phase one trials, in general ,are truly very early investigations. So, one example of a phase one trial that was done several years ago was looking to see whether, if we actually injected umbilical cord blood stem cells directly into the bone marrow, would the patient's blood counts recover more quickly. And so that was an example of a phase one study because it wasn't clear how well a patient is going to tolerate having the stem cells infused directly into the bone marrow. It may be a new drug that we're going to be looking at as to whether or not this is safe in a transplant patient. So, this may be a drug that is already FDA approved, it may be on the market for another indication, but we want to examine it in transplant patients.

(00:13:04): Efficacy is measured when we're doing a phase one trial. So, we are looking not only at how well someone is tolerating a new investigation or how safe it is for the patient, but we are going to look at how well it's working.

(00:13:24): Phase two trials evaluate the feasibility, acceptability, and affordability of the intervention for the broader patient population. Do we want to investigate this in subsequent patients, because phase one trials generally involve very small numbers of patients, usually less than 25 patients? Phase two trials are probably the most common trials that we find in oncology as well as in transplant. And this is generally looking at the initial assessment of how well something works. We've already determined that this is safe and that the patients can tolerate it, but does it really have the benefit for the patient that we expected it to have? And so this gives us an early look at how well this investigation may work.

(00:14:20): It also gives us some ideas of how acceptable this is both to patients and providers because feasibility is key. So, if there's something that may work fantastically but you're having to live in the hospital, that may not be an optimal outcome. And so we want to be able to look at efficacy. at least preliminarily.

(00:14:52): We also look at cost because realistically if we're not getting enough benefit to the patient compared to what we think is our standard historical control, if the compound, the drug or the intervention is going to cost $400,000 but the standard is only a hundred thousand dollars, that is something that is important when we look at these studies as well.

(00:15:27): But phase two trials, as I mentioned, are to obtain really more information also about how well a patient is going to tolerate this, but we don't want to expose a large number of patients to something that may be toxic or may not provide much improvement over the current standard. So, these phase two trials are usually also relatively small in number and may be up to 40 patients, it may be up to a hundred patients. It's going to depend upon the question that we are trying to ask as that primary endpoint. So, there's a lot of statistical analysis that goes in as we're designing these trials to make sure that we are not overexposing patients or putting patients at risk for something that isn't going to potentially provide them benefit.

(00:16:20): Phase three trials are randomized comparisons of an intervention group and a control group.  Phase three trials. So, I wrote on here that phase three trials are always randomized. That is true 99.9% of the time. There has been one trial within the transplant field in the past decade that was considered a phase three trial but patients were not randomized. And the reason that was done, and it's specifically for a compound called defibrotide that has been used to treat patients with veno-occlusive disease of the liver and the trial itself was designed to only enroll patients who have very severe VOD. And so because they had severe VOD and there was no other acceptable alternative, none of the physicians who were investigating and participating on this trial were willing to do that. So, we ended up doing something that we used as a historical control. But in general, these are randomized studies to compare a new approach to the standard approach. It may also compare two new approaches that appear to be similar in their outcomes, particularly if there is not a standard. So, these are all important things to know and to ask questions about when you're talking to your physician.

(00:17:57): Randomized or blinded trials reduce unconscious bias that can skew outcomes. We're going to talk about some of the words that people always get frightened about when we talk about randomization in phase three trials including words like blinded and placebo controlled. The rationale behind using blinding and placebo controls is to make sure that we're really measuring the true benefit of the intervention as opposed to how the physician or the patient is perceiving the benefit because we want it to be better. So, it helps to remove some of the unconscious bias that may be there. It also helps us to better assess any side effects from an intervention. These are usually very large trials and tend to enroll several hundred patients and generally are multicenter national clinical trials often done by either pharmaceutical companies if it's a drug that's being tested specifically or more commonly in transplant being conducted through the blood and marrow transplant clinical trials network.

(00:19:19): So, randomization means that I, as a physician, and you, as my patient, don't get to choose which arm of the study that you're on. And the reason for that is to try and help balance out specific features that the investigators may not have considered. So, it helps to balance out those patient characteristics, disease characteristics, transplant at different centers, those kinds of things. But it is to remove bias so that we can get a true measure of how well the intervention is compared to the standard. And it's generally done using computer algorithms but it's very similar to thinking of drawing a number out of a hat, only you don't know when you get that number which arm you're going to be randomized to, particularly if we're doing something called a placebo controlled or blinded trial, which we'll get to in the next couple of slides.

(00:20:26): Patients may also be stratified into sub-groups in a phase three trial. The other aspect of randomization is that we use a scientific statistical term called stratification, which means that if there are several different centers within the trial, we may decide that we want to stratify patients by center. So, you're essentially being randomized within your own transplant center. It may mean that we are randomizing based on the conditioning intensity, so if we're looking for something as an outcome to improve graft-versus-host disease prevention, we may say if a patient is getting reduced intensity conditioning, we know there's a little bit of a difference between reduced intensity conditioning and fully myeloablative conditioning for GVHD. It's relatively minimal but it may have an impact in the setting of a GVHD prevention trial. So, we may randomize the group of patients that are getting reduced intensity in a separate stratification than the patients who are getting the myeloablative conditioning.

(00:21:45): Blinding means neither the patient nor the doctor knows which group a patient is in.  Blinding is generally used when we're adding a new drug to a standard of care treatment. So, for example, if we think that tacrolimus and methotrexate is the standard graft-versus-host disease prevention and we want to know if drug A added to that backbone of tacrolimus and methotrexate may be better, we would want to be able to blind both the physician and the patient from knowing which one is getting drug A and which one is not. And it's because we want to remove that bias of expecting something or seeing something that may not be there.

(00:22:39): Placebos are non-active substances that clarify whether the intervention is more effective than the placebo. Or more importantly also we want to make sure that we're not introducing increased side effects or be more likely to identify or report side effects if you have them on the drug A being investigated. So, that's where placebos come in and placebos are truly a non-active substance. Most people will think about that as "the sugar pill". Really what a placebo is designed to do is not have any interaction with you, the patient, or with any of your other medications, but it will look exactly like the compound that we're investigating.

(00:23:24): So, if drug A is a pill in my previous tacrolimus methotrexate example, if drug A is a pill, we'll have a placebo pill that looks exactly like it and that way both the physician and the patient won't know whether you are getting drug A or placebo in addition to that standard backbone . That’s so we can make sure that we're being very consistent in reporting outcomes, results, side effects that the patient may be experiencing. So, that's the purpose behind using placebos.

(00:24:06): Even with placebos, clinical trials for transplant patients almost always involve active treatment as well. In the setting of placebo trials, particularly in transplant, it is very unlikely that you're not going to also be receiving an active treatment. So, generally if we're talking about treatment of graft-versus-host disease, it may be prednisone plus drug A versus prednisone plus placebo. Prednisone alone would be the standard of care in both arms of that trial. The patient will receive that standard of care, but the question is whether drug A adds to the prednisone to better treat it.

(00:24:55): A patient’s eligibility and quality of life are also evaluated before they enter a clinical trial. In general for clinical trials, we have things called eligibility. This differs in strictness by the phase of the trial and by the intervention being studied. Eligibility is something that is important for us to know whether a patient is meeting all the criteria to be on this study. And those eligibilities have been designed by the study investigators to make sure that we are treating the patients that we think would have the most benefit from this investigation.

(00:25:36): We also will have specified visits that may be required for people participating on a clinical trial. These may be more frequent than if you were not treated on a clinical trial, but not always, and that's an important question that you're going to want to ask as well.

(00:25:53): And finally, many clinical trials will also have specific questionnaires to try and ascertain how this intervention is affecting a patient's quality of life. You're going through transplant to get better, to get back to that normal life. We do not want to make that quality of life worse by the intervention that we're studying. And these questionnaires are very important for us to be able to understand how both the standard therapy as well as the investigation is impacting you.

(00:26:38): Clinical trials are scientifically rigorous investigations that are carefully reviewed by other researchers and experts. Most patients are concerned that they are being experimented upon and there's no question that a clinical trial is an investigation. It is an experiment in the sense that we are comparing two things, but we're doing it in the setting of scientific rigor. So, a clinical trial will have a lab-based background that makes it rational to proceed. Depending on the phase of the trial, it may already, been explored in a transplant patient and have some information about that as well. It is designed by people who are experts in the field and for many of the BMT clinical trials network trials, there is a steering committee that reviews and vets all these clinical trials before they ever go to all of the regulatory boards to make sure that we're going to be doing this in the safest and best way possible for our patients.

(00:27:58): It also requires review by other researchers, so individual cancer centers and transplant centers will also have a specific scientific review that's required before the trial will be allowed to be opened at that center. Here at the University of North Carolina, we have a protocol review committee that requires scientific approval for a clinical trial before it ever goes to something called an institutional review board, which is specifically an ethical review to make sure that no patient's rights are being violated, that we're not increasing harm to the patient. And our institutional review boards will have patient advocates involved. At UNC our protocol review committee also has a patient advocate involved looking at whether it may be requiring multiple extra visits that can impact patients as well and whether or not those are reasonable for what's being investigated in the trial.

(00:29:14): Once underway, trials are carefully monitored for any adverse events. Once the trial has been approved at a center and is open, there are going to be ongoing data and safety reviews. So, toxicities are looked at, at a regular time interval, as well as any specific serious adverse events or serious toxicities or side effects are looked at generally within 24 hours by a central Data Safety Review board. Sue mentioned that I am a medical monitor for the BMTCTN. I review safety toxicity for clinical trials that are not open at UNC, so that it's not introducing my bias of wanting the trial to stay open. So, medical monitors reviewing these generally don't have patients on the trial so we can be truly objective about those toxicities.

(00:30:19): Highly successful trials may be terminated early so all patients can receive the newly successful intervention. Phase three trials often will have something within the clinical trial that is designed to look at the blinded data to look at efficacy. How well is this intervention working? Are we making things better for the patient or in this case does one arm look much better for that primary goal of the study than the other arm does? And if it does, and they're looking at this blinded data, the Data Safety Monitoring Board may say it is not appropriate to continue this trial. Because arm A looks so much better than arm B, we should not be continuing to treat patients on arm B. And so, these things are done to make sure that we are keeping our patients as safe as possible while still being able to improve transplant outcomes.

(00:31:19): Informed consent means patients get a detailed consent form to study and ask questions before agreeing to join a trial. So, informed consent. If any of you have participated in clinical trials, you will probably remember a very lengthy document that has a lot of information about what's going to happen to you in the trial, potential side effects of the trial, things that may be occurring differently if you were in the trial or not in the trial. The key is that informed consent isn't that piece of paper. It requires discussion between the physicians and their team and the patient and their family and friends who are supporting them.

(00:32:06): So, it's very critical. We continue to try and make consent forms more reader friendly yet still have all the information available, but it's still a complicated document. So, it's important to have a consent form, to read it, to make notes on that consent form so that you can ask specific questions. That's your copy. Then, if you decide to participate, there's going to be a clean signed copy and you'll also have a copy of that, but this is your working document to make all those notes, ask your specific questions, have family and friends read that consent form and write down their questions as well.

(00:32:55): So, what I wanted to give you next was a series of useful questions, things I try to address with my patients when I'm talking about a clinical trial. But oftentimes we all get sidetracked by additional conversations and so the things you want to make sure you have answers to are going to be:

(00:33:16): Patients should clearly understand the purpose and primary and secondary goals of a trial. What's the purpose of the trial? What is the primary goal of this trial? Is it to see whether, this is very early, so is it just to see if I can tolerate this drug or are we looking at something that is moved along in that clinical experimentation to move it forward and have evidence that it works and we want to further strengthen that evidence?

(00:33:45): We also want to know what those secondary goals are for that trial when you're participating. It's going to impact some of the things that are ongoing for you in that participation including maybe how frequently you're being followed.

(00:34:01): Patients should also be informed about the logic behind the trial and why a particular intervention is being tested.  You want to know what prior information led to this clinical trial being performed, what is that science? What was the reason that you think this is important for me to participate in and what else has happened?

(00:34:15): How many patients have been treated on this trial or how many patients were involved leading up to this trial? What were the outcomes in that situation?

(00:34:29): And sometimes that information may not be available and so we give you all of the information that we have and in those early phase one clinical trials, we may not have other experiences with that particular intervention, but we know from the science that's been done that it appears to be reasonable to proceed.

(00:34:56): Patients also should understand the different treatments and obligations (like the number of clinic visits) in each arm of a trial.  I think one of the big things is to make sure what's the difference between ... how's my treatment going to differ if I'm on this clinical trial or if I decide not to be on this clinical trial or for whatever reason am not found to be eligible to participate in this clinical trial. What's the difference going to be in my treatment? Am I still going to receive the same chemotherapy but now have potentially fewer visits, because I don't have study specific visits? Or if I participate in the trial, am I going to have to have an extra bone marrow biopsies or extra blood draws ? Or how many of those questionnaires am I going to have to fill out? And so those are the things that you want to make sure that you've asked before you consent to participate in a trial.

(00:35:51):  How is my information kept safe? When we are conducting a clinical trial, we are going to be collecting data on the patient. Patients are assigned a study number and so with that study number, that's how the information is tracked. But within your own transplant center we are going to have access to that study number. Medical monitors who may come to our clinical trial monitors if this is particularly a pharmaceutical company, may come to review that data. Ask how that data's going to be kept, how your personal information may be kept safe.

(00:36:35): One of the other things that's important is new information in terms of the trial. I mentioned a data safety monitoring board may say, oh, arm B doesn't look as good as arm A, so we should stop accruing to arm B. Aside from being told that this trial is ending, you need to know why. And so you need to be able to ask, you need to know who's going to tell you where if new information or new risks or things like that come out from this clinical trial.

(00:37:09): If new risks emerge during a trial, changes may be made and new consent forms be issued. And in general, with those, if we find new significant risks in monitoring the safety of a patient, what's going to happen is that the informed consent document is going to be revised and you're going to be asked also to sign that new consent form.

(00:37:26): Payment for clinical trials is complicated and may not always be covered by insurance. Payment for clinical trials. This is something that is definitely a complicated issue. Insurance companies may or may not cover specific costs related to hospital stays or other issues related to the trial. And so getting information from your center about whether or not your insurance company has looked at this and said, 'yes, I'm still going to pay for transplant even if you participate in a clinical trial', and this is something that can happen. We find this particularly frequently with Medicaid patients that they may not be eligible to participate in one of those early phase one trials, but it's okay if it's a later phase two or phase three trial. And so those are going to be questions you’re going to want to be aware of as well.

(00:38:38): Patients are also entitled to know the length of a trial, what happens if it closes, and who to contact for ongoing information about the trial. It's important to know how long you're going to be on that clinical trial. Are you going to have to be following up every six months? Are you going to have to be following up for the next five years? In transplant this is not nearly the same problem simply because most patients are following up frequently at their or regularly at their transplant center even a few years out from transplant. But for some drug trials this may be an important piece of information.

(00:39:18): What happens if the trial closes? This is going to be particularly important for certain drug studies. So, for example, if somebody is enrolled in a clinical trial that's looking at a drug for trying to prevent the relapse of their cancer and they're doing fine with the drug, they're tolerating the drug, but the study closes, are they still going to be able to get that particular drug? And that's something that you would want to be able to know what is that situation. And most clinical trials have a provision in there in the event of those and if a trial closes. And so that's something you'd want to be able to ask.

(00:40:11): Who do you talk to if you have questions or concerns while you're on the study therapy? First and foremost, always talk to your physician. Go first to the physician who is generally also involved and aware of what's going on with that clinical trial. There will be a principal investigator at the transplant center that you're at for that specific clinical trial. It may or may not be your transplant physician. That's someone that you can talk to. The clinical trial coordinator who you're interacting with or the research nurse that you're interacting with. All these people you can talk to about questions or concerns while you're on study therapy. Our goal is to treat you as a patient, and if you have concerns and say I don't want to do this anymore, that's okay. You always have the right to say, 'I don't want to participate in this trial anymore'. And so that's something that you want to make sure you're having good communication with your physician.

(00:41:18): Doctors may propose joining a clinical trial at different phases of treatment. Physicians are going to talk to you regarding potential trials generally at the time of specific treatment decisions. So, this may be pre-transplant, which can be a very scary thing. You're being referred to a transplant center because you have a disease for which transplant is required or recommended and your transplant physician talks to you about transplant but also says, 'we have this clinical trial for which you may be eligible' and that can become a lot of information, which is why a webinar talking about clinical trials is very important.

(00:42:06): Your physician may talk about a clinical trial at the time of development of specific complications. So, if you develop acute graft-versus-host disease, we may have a clinical trial that's available for treatment of acute Graft-versus-host disease or we may have a treatment trial available for somebody who has chronic Graft-versus-host disease or who develops a specific infection. And so your physician may say 'you have developed acute Graft-versus-host disease. The standard treatment that we use is prednisone. We have a trial that's looking at prednisone alone, which is standard, versus prednisone plus drug X' and then talk to you about whether you want to participate, give you a lot more details, give you that piece of paper with the consent form to help review, let you talk to the clinical trial coordinator, answer all those questions.

(00:43:12): But patients can also search for trials and searching for trials can be a very overwhelming and complicated task. But there are certainly websites that talk about clinical trial availability and the one that is most common within the United States is something called This is for every clinical trial regardless of disease or whether it's even, it could be a trial for diabetes or a trial for eczema or something like that. So, there's this what we call a search engine very similar to Google or Bing or any of your other search engines. But the key is making sure you talk about those also with your physician because you can do a search engine looking for Graft-versus-host disease and within that search engine it may pull up all the trials that are also having Graft-versus-host disease as a secondary endpoint as opposed to a treatment for Graft-versus-host disease.

(00:44:28): Patients can also search for clinical trials at So, those are important things to try and when you're weeding through those to make sure that you do discuss those things with your physicians as well. The is the website for the blood and marrow transplant clinical trials network and on the public website that's available to everybody, you can actually look at the clinical trials that they have open. The BMTCTN has enrolled more than 9,000 transplant patients on transplant trials since 2002. And so that information about the different trials that have been done is available as well. Your cancer center websites are going to be a very important place for identifying potential clinical trials as well.

(00:45:25): There may be trials that are not available where you live and if that trial is not available where you live, then that's going to unfortunately require you as a patient traveling to where that trial is open to find out whether you're eligible. And that's something too, to discuss with your physician because your physician may be able to make a phone call to find out whether you may be eligible for that trial. It's important to get as much information as possible.

(00:46:06): Like I said, you want to read the consent form, you want to talk to the clinical trial coordinator. Sometimes you may not want to talk to the physician because you may feel that the physician wants you to participate in this trial. No physician is going to try and pressure you into participating in a clinical trial. It's always presented as an option. This is what is going on in this is why we think this might be of benefit to you and here's why.

(00:46:45): Getting second opinions or different input can be important in deciding whether to join a trial or not. But if you want to talk to somebody where you're not feeling pressured, then you should talk to a clinical trial coordinator, a nurse, a friend, your primary care physician may be somebody that you can also talk to get a different perspective.

(00:47:05): Once you've consented to the trial, then we have to confirm that you are actually eligible. And that goes back to those eligibility criteria that we talked about. In general, for most of these transplant clinical trials your physician has, even before presenting the trial to you, will at least look and say, 'yeah, I think you're probably going to be eligible for this', but final eligibility can't be determined until after you have consented to participate in that trial.

(00:47:45): Also, sometimes there may be specific testing that's required. So, there's an ongoing clinical trial right now for patients with a specific type of lymphoma and receiving an autologous transplant, but we have to be able to send off a biopsy - it could be from when you were first diagnosed - but we have to send off a biopsy to get special testing done on that biopsy to confirm that you will be eligible for that trial. And oftentimes, in those situations, there' are essentially two consent forms. You have one which is called a screening consent form, and then if you're found to be eligible then you'll sign the second consent form, but you can review both of those consent forms before you ever sign that screening consent form.

(00:48:39): As I mentioned earlier, study treatments and participation in clinical trials may require certain extra visits. Oftentimes it's not substantially more than what you are doing as a transplant patient anyway, but sometimes it is and that's something that you want to discuss with your physician and with the clinical trial coordinators, 'how frequently am I going to have to be seen specifically related to the clinical trial?'

(00:49:10): Patients may stop participating in a clinical trial if they have adverse effects or no apparent benefit. The other thing that is important is that even though you are participating on this clinical trial, you may have to stop that study treatment earlier than you've expected. You may have developed side effects or toxicities that don't resolve enough for you to continue on the clinical trial or you may, if it's a trial looking specifically to treat Graft-versus-host disease but your Graft-versus-host disease isn't improving substantially, then we may say we're not going to continue on the trial due to lack of benefit.

(00:49:59): When study treatment ends we do continue to follow patients until the trial is completed. It may be less visits or it may be phone calls. But you as a patient always have the right to say, "I am no longer on this trial. I do not want to be followed anymore related to information on this trial and please withdraw my consent for future follow-up." That is your right as a patient, you do not have to be followed for the full length of the trial if you decide that you no longer want to participate.

(00:50:38): Clinical trial participation is an option for the patient to decide. So, just to briefly summarize and let everybody get time to get their questions answered, clinical trial participation is a decision, it's an option. It's something that will occur or should occur out of discussion between you, the patient, and your physician.

(00:50:58): The key piece that I want patients to get out of this is that clinical trials, while considered an experiment, are carefully designed. They have a scientific rationale behind them. The patients are closely monitored and patients participating in the trial are steadily examined in order to ensure safety to the patient. But this is all to try and improve outcomes both for the current patient, you, who's participating on the trial but also for our future patients. And with that I'm going to stop and allow questions.

Question and Answer Session

(00:51:45) [Susan Stewart]: Thank you very much Dr. Riches. That was a great presentation. So, we have a couple to get started. "What percentage of a trial is typically getting the placebo?"

(00:52:15) [Dr. Marcie Riches]: That's a great question. That's going to be something that is going to differ based on every trial and that's going to be a question when we talk about randomization. A randomization could be something that's a one-to-one randomization, meaning that it's a 50/50 chance that half the patients will get placebo, half the patients will get the drug being tested. It could be a one to two randomization, meaning that in every three patients, one patient is getting placebo and two patients are getting the active treatment. And that's a question that's based and determined based on the statistical endpoints that we're looking for in the trial and how much information we need to acquire. And so that is another good question to make sure that you are asking when you're being approached for a clinical trial to make sure.

(00:53:21) [Susan Stewart]: How can someone participate in a trial that is out of state? Her state has very few trials available.

(00:53:30): [Dr. Marcie Riches]: So, that in general does require travel. Clinical trials may not be open at every single transplant center or you may not have, as you've pointed out, a large number of trials within the state in which you live. And so when you're investigating or your physician is investigating, what trials are options, if there is a trial for which you may be eligible and you are interested in potentially participating, you may have to travel to that site.

One of the things that is very active, and I'm sure most of you are familiar with it now, are things looking at CAR T-cells. And CAR T-cells for treating different diseases like ALL or lymphomas are not going to be done at every center in every state, and so that will require travel. So, here at UNC we do have some CAR T trials and we have patients coming from all over the country to potentially participate in those.

(00:55:03) [Susan Stewart]:  Is there a best place to search for clinical trials related to fertility following transplant?

(00:55:10) [Dr. Marcie Riches]: That is going to be from a transplanter's perspective, I will be very honest with you, that's not something that we do the best job at focusing on for patients. That would be something that knowing what's available, I would actually refer you to and do a search, but I would also talk to your OB-GYN or your urologist for the men to talk about whether or not there may be trials available for that specifically.

(00:55:51) [Susan Stewart]:  Are you ever paid to participate in a clinical trial or have your costs taken care of?

(00:56:01) [Dr. Marcie Riches]: That's always a complicated question. In general, it's going to be specified in the consent form. Often times there may be, for some of these trials that are including surveys for quality of life, there may be some small payment like a gift card or something like that for your completing the questionnaire. However, it is it not something, in general, that patients are paid to participate, particularly within transplant clinical trials.

In terms of drug costs, the drug may be supplied and that's going to depend on whether or not is there pharmaceutical company support of the trial and it may be a support that's "an in-kind support", meaning they give you free drugs but they're not actually managing the trial. And so those kinds of situations can occur where there is some sort of remuneration.

(00:57:24) [Susan Stewart]:  How do I tell whether a particular clinical trial is worth participating in? How can I tell the difference between a good trial and one that's not so good?

(00:57:36) [Dr. Marcie Riches]: That's a question that you need to point-blank ask your physician. I will tell you that when trials are being considered at an institution, there's a lot that goes into whether or not a center is going to open a trial. They're going to look at, does it make sense scientifically? Is it something that we think is going to be optimal for our patients based on the types of patients that we see on a regular basis? Most trials that get to the point of actually being opened within an institution have gone through scientific review, have gone through ethical review through an institutional review board. It's very unlikely for a less good trial to be opened.

(00:58:42) [Susan Stewart]:  Does the hospital determine what clinical trials they offer, participate in or do the drug companies make this determination?

(00:58:51) [Dr. Marcie Riches]:That is a little bit of both. So, a pharmaceutical company may reach out to a center and say, "Are you interested in participating in this trial?" But ultimately a center is going to make the decision about what trials they will open. So, it truly falls within the center to make that final decision. But a pharmaceutical company may reach out to a particular center because that center has a particular expertise or a particularly large patient population that may be appropriate for that specific drug trial.

(00:59:43) [Susan Stewart]:  What importance does age play when clinical trials are being set up?

(00:59:48) [Dr. Marcie Riches]:That depends very much upon the intervention being tested and what that primary endpoint is going to be. A good example of that is one of the BMT-CTN trials that was looking at using umbilical cord blood transplant and the question was whether or not there was a difference between a patient who received just a single cord blood unit versus a person who received two umbilical cord blood units. Because there is a limitation in the number of cells that we can have from a single cord blood unit, that trial was predominantly a pediatric trial because they're generally much smaller individuals.

Older age also can play a role in clinical trials because if we're investigating an impact of conditioning intensity, so we want to look at does a myeloablative conditioning regimen A versus myeloablative conditioning regimen B, is one better than the other, and in general, we may not be doing a myeloablative conditioning regimen for somebody who's 65 years old and so that may be limited, has some age limitations. So, there's going to be various factors that go into this. A lot of drug trials may not have pediatric patients eligible for them because the drug hasn't been examined in pediatrics yet. And so those are all various things that go into that age criteria.

(01:01:52) [Susan Stewart]:  How long does it take to set up and get approved for a trial in a hospital or university?

(01:02:14) [Dr. Marcie Riches]: For participation. That is going to depend upon sort of the eligibility criteria for the trial and if there's specific testing that needs to be done or is it something that we need to send a sample away to be tested, such as the lymphoma trial that I mentioned. But in general, if we are looking at somebody for a clinical trial, we are looking to enroll them usually within the next two or three days. But if there's special testing that needs to be done, it may be two to three weeks, so it's going to be very different. But depending upon the trial that's being looked at, and that's a good question to ask your physician is, okay, if I want to participate in this clinical trial, when do I start therapy?

(01:03:11) [Susan Stewart]:  Why would a patient be told they are too healthy to participate in a trial when the drug they're on might be working, but the side effects are affecting quality of life and putting the patient in bed?

(01:03:28) [Dr. Marcie Riches]: So, I'm not sure I fully understand the question. The too healthy to participate part, it may be related to the disease. So, if it's a drug that's looking at treatment of myeloma for example, and the myeloma is well controlled, then from a disease standpoint you may be too healthy to participate in that trial because it requires the myeloma to be progressing. I'm not sure if that answered the question. If it didn't, I apologize. And if you can add more information, I'll try and address it.

(01:04:22) [Susan Stewart]:  Do you have to live in the state where the trial is going for the entire trial or might it be worked out where you have some of the treatment done in your home state?

(01:04:34) [Dr. Marcie Riches]:That's going to be again, dependent upon the trial itself. If it's a pharmaceutical company trial, whether or not the pharmaceutical company is willing to have your local physician give you study drug or study drug can be mailed to you, you will end up having to travel back and forth to the primary site for that trial. But sometimes those things can certainly be arranged. And I know certainly there are trials that were ongoing. I used to live further south and would get snowbirds. So somebody was on a trial where they lived in Chicago, but they are then moving to Florida for six months for the winter and so we can try and coordinate that way. So, it's certainly potentially something that can be done, but it's going to require significant conversation both with the study center as well as your local treating physician.

(01:05:59) [Susan Stewart]:  Can you enter a trial after it is started?

(01:06:02) [Dr. Marcie Riches]: Absolutely. Trials generally have an ongoing accrual. So, it's not that on day one we automatically enroll 300 patients. This is oftentimes something that's going to be open and we start accrual and this trial is still accruing, so there could be 50 patients on the trial, but we need 250. This will be an ongoing, what we call a rolling accrual.

(01:06:35) [Susan Stewart]:  Can I find out in advance how patients who are already on the clinical trial are doing as far as side effects and cure?

(01:06:46) [Dr. Marcie Riches]: Not in general, not necessarily, unless there has already been what we call an interim analysis. The toxicity issues will definitely, if it's a significant toxicity, that information will be available, because it has probably resulted in a change in the consent form. But even as the people running the clinical trial, we only know what's going on with our patient. We may only know what's going on in terms of efficacy in our patients that we have locally, but don't know what's going on at all of the other centers around the country until those results are also published.

(01:07:34) [Susan Stewart]:  What happens if a bad side effect happens while I'm on the clinical trial? Who pays to fix it?

(01:07:41) [Dr. Marcie Riches]: So, again, that's part of the reason that we talk about making sure that your insurance company is aware that you're participating in a clinical trial. And that's going to be in your consent form as well to talk about in the event of a toxicity, what's going to happen to me. And in general, it's your insurance company that is going to cover those costs of you being hospitalized or requiring a treatment for a side effect.

(01:08:27) [Susan Stewart]:  Is there a way to find out the results of the clinical trial that has ended? When you check on the clinical trial website, there's a dropdown for results with this very, very seldom anything there, even when the trial end date has long passed.

(01:08:41) [Dr. Marcie Riches]: So, I think part of that is, often, because the end date may actually be the end point for accrual, meaning that the trial is no longer accruing patients, but patients are still being treated and followed on the study. And so no results are necessarily available, because the analysis for that has not yet occurred. So, that's generally why you won't see those results.

(01:09:10) [Susan Stewart]:  Are trials available on for patients from another country other than the US?

(01:09:17) [Dr. Marcie Riches]: So, the trials are there. Again, it's going to be an issue of are you able to participate in the trial either using your self-paying care if you're coming from another country or you purchase an insurance when you come to the US that would allow you to participate in that trial. But in general, it's going to be based on whether or not you are able to come to the US to participate in that trial and have the funds to help support you if you don't have insurance.

(01:10:11) [Susan Stewart]:  If I participate in a clinical trial, do drug companies get access to my personal information?

(01:10:18) [Dr. Marcie Riches]:That's an excellent question and the information they will have on you is a study number. They will not have the ability to contact you, they won't have that personal information. There will be, in general, pharmaceutical companies contract with something called a clinical research organization or a CRO and they monitor the data that's being submitted. So, they're coming to the transplant center or the cancer center and monitoring what's going on or are the visits happening appropriately, are side effects being reported appropriately? They may actually, they very well may see your name because often they're having to look at your medical record, but what they're allowed to look at is limited. And with our electronic medical records, we can block certain things like demographics, they can't get access to where you live and your phone number and things like that but can look at the notes that the physicians or providers have written or your lab results. Pharmaceutical companies do not have any access to that information and the pharmaceutical companies themselves do not come to the center. They always go through a clinical trial research organization.

(01:11:56) [Susan Stewart]:  My husband has multiple myeloma, but they say his numbers are not high enough to put him on a trial even though they're going up, the drug he's currently on is working, but the side effects are not allowing him to walk.

(01:12:10) [Dr. Marcie Riches]: So, in interpreting that it means that at this point they don't have a clinical trial for which he is eligible, because his disease hasn't progressed enough. If he feels that he's having side effects from the drug that he is on, talking to his physician about, 'I'm not able to tolerate these side effects, can we stop this therapy? Is there something else we can try?' Is a discussion that you absolutely need to have. And so in that situation, it sounds like they are talking about the disease. The myeloma disease hasn't grown enough for you to move to that clinical trial, but that doesn't mean that you necessarily have to stay on the same drug and that's a discussion you need to have with your physician.

(01:13:13) [Susan Stewart]:  What do I do if my insurance won't pay for a clinical trial? Is there any other way I can participate?

(01:13:20) [Dr. Marcie Riches]: Unfortunately, the short answer is no, unless you have a substantial fund of money, because that's something that is going to end up being required to cover any potential side effects that may occur. Sometimes if it's a pharmaceutical trial, they may say the pharmaceutical company may be willing to do something, but that is by no means a routine thing.

(01:14:08) [Susan Stewart]:  'When I look on at trials that are many years old, I can't find the results and even when I emails the principal investigator, no one ever gets back to her. What would you suggest?'

(01:14:24) [Dr. Marcie Riches]: I actually would at that point suggest, and this is going to sound silly, but Google is a very wonderful search engine. You can actually, if you have the title of the trial from, you can Google that title and if any results have been published either in something called an abstract form, meaning some of it was presented at a meeting or it was, the paper has already been published, the website may not have been updated, but the results are out there in the public domain.

The other thing that's important to know is that, unfortunately, a lot of times those trials that don't have the outcome that we want, what we call a negative trial, something where it didn't work as well as we wanted it to, those are very difficult to get published in standard medical literature. So, oftentimes those results don't necessarily make it out into the public domain.

(01:15:40) [Susan Stewart]:  A patient suggests using Google Scholar for when looking for information about clinical trial outcomes.

(01:15:51) [Dr. Marcie Riches]:That's certainly fine.

(01:15:58) [Susan Stewart]:  'With the increasing popularity of CAR T-cell therapy, do you eventually see CAR T-cell therapy eliminating the need for bone marrow transplant?,

(01:16:09)  [Dr. Marcie Riches]: I think that most definitely, the jury is still out on that. Most of the CAR T data are in people who either weren't eligible for transplant or already had their diseases relapse after transplant. And so to say that this is going to be something that gets rid of transplant in the future, I don't think we know that yet. I don't think that there is enough information available.

The first publications for CAR Ts truly came out seven years ago, and so it's certainly something that as a transplant physician, I would be thrilled if I never had to transplant another patient, because CAR Ts fixed everything. But I don't think that that's something that we can certainly say right now without having subsequent clinical trials of looking at CAR Ts in early therapy as opposed to much later therapies where they've been tested and gotten their FDA approvals.

(01:17:26) [Susan Stewart]:  All right, so before we wrap up, I do want to point out one new resource to patients to help them with their clinical trials search. Be The Match, which is the agency that finds bone marrow, stem cell, and cord blood donors for patients who need a transplant, has launched a new initiative called the Jason Carter Clinical Trials Program. And the program consists of two services and the first one I think is the most important. It's one-on-one support for patients and families to help them answer questions and guide their clinical trials search. A nurse navigator can help you identify trials that might be appropriate for your consideration and discussion with your doctor, explain to you clearly what the trial would entail, and help you contact the lead investigator on the trial if you want to do that.

(01:18:16): Eventually, the program is also going to have an online database. There's a work in progress database up there at the moment that will list clinical trials to treat various conditions, Graft-versus-host disease, various diseases, et cetera. At the moment, the database contains some, but not all of the clinical trials out there to treat various diseases and the side effects of transplant. And the search tool that you would use to search for trials is still undergoing refinement, so it doesn't get you the cleanest list of trials that meets your search criteria. So, at the moment, I would strongly encourage you to contact the clinical trial patient education specialist, who can give you personalized service and help you look for clinical trials that might be appropriate for you. And the phone number is there on the screen. It's (888) 814-8610, or you can email him at

(01:19:24): Closing. So, I want to thank everyone, Dr. Riches and everyone who participated in the Q&A for helping us discuss this very important topic this evening. If you have questions and want to follow up with us, please do email us at, or you can call us at (888) 597-7674.


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