Clinical Trials 101 - Why They Are Important and What You Should Know

Transcript of Presentation.

(00:00): [Susan Stewart]: Welcome to the workshop, Clinical Trials 101: Why They Are Important and What You Should Know. My name is Sue Stewart, and I will be your moderator for this workshop. Before we begin, I'd like to thank Sanofi and Bristol Myers Squibb, whose support helped make this workshop possible.

(00:19): Speaker Introduction. It's now my pleasure to introduce today's speaker, Ms. Caitlin Guzowski. Ms. Guzowski is the Clinical Research Manager for the Blood and Marrow Transplant, Leukemia, and Cellular Therapy Programs at Northside Hospital in Atlanta. She's currently responsible for bringing new and innovative clinical trials to Northside patients by developing relationships with pharmaceutical companies so that patients can access the latest treatments for their blood cancer. Please join me in welcoming Ms. Guzowski.

(00:57): [Caitlin Guzowski]: Good afternoon, everyone. It's a pleasure to meet you all. Thank you for attending our workshop today. I have been working in the clinical research area for 14 years – 12 of those years have been at Northside Hospital. I started out as a Research Coordinator and have been the Manager of the program for the last two and a half years. I am primarily responsible for regulating our clinical studies from start to finish. I take part in getting the trial up and running from the very beginning, and working with the trial sponsor, our clinical research coordinators, and our nurses until the very end of the trial. I also help manage the day-to-day activities of our research personnel.

(01:50): To provide some background on the research program at Northside Hospital, we are a small subset within a larger umbrella of the Central Research Department. We have a robust pipeline. We have approximately 75 open clinical trials for all our patients, spanning various phases of clinical trials. They include different diseases and different interventions for blood cancers. I work with 6 physicians and we have 14 research personnel to identify potential patients for our research trials. Our physicians are extremely involved and are very pro-research at our program, as clinical trials can change the standards of care.

(02:27): Overview of Talk. The four basic questions regarding clinical trials that will be discussed today are ‘how’, ‘what’, ‘why’, and ‘where’. My hope is that everyone will gain a deeper understanding of what clinical trials are all about, and why they're so important for cancer treatment development.

(02:48): The first four questions we will address will describe what clinical trials are. What exactly is a clinical trial? What are the phases of clinical trials, and what do each of those mean? What is the purpose of a clinical trial, and what does it do? What happens during a clinical trial as a participant? For example, what am I going to be responsible for? What am I going to be doing? What is the clinical trial?

(03:19): The National Institute of Health defines a clinical trial as a research study in which one or more human subjects are prospectively assigned to one or more interventions to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. In other words, patients participate in a research study that provides them with treatment. Then, the scientists who are participating in that study review the results to determine how that treatment affects patients' bodies and what the outcomes of those patients are.

(03:56): The most important part to remember about clinical trials is that they are optional, completely optional, and voluntary. Patients are given all the information about the clinical trial up front, and then they can decide on their own whether or not to participate.

(04:12): There are clinical trials where healthy volunteers are needed, and others where there are specific diagnoses or diseases that are required. For our talk today, I'm just going to focus on the blood cancer clinical trials, the questions that these trials pose, and the answers that we're trying to get.

(04:29): If you recall your middle school and high school science classes, you likely learned about hypotheses and the process of trying to prove them. Clinical trials do just that. They attempt to answer questions posed by scientists.

(04:46): We' hypothesize’ that this drug will kill certain leukemia cells. We administer the drug to the patient, gather information from laboratory tests, scans that you can undergo, any biopsies, and information about side effects that you experience, and analyze these results to either prove or disprove our hypothesis.

(05:08): We're always trying to answer new questions or come up with new ways to prove our hypothesis correct – new technologies, new innovations, and research – so we can get better at preventing, detecting, diagnosing, and treating blood cancer. Most importantly, we want to improve patient outcomes. That is the goal of a clinical trial – to get rid of the cancer and enhance patient outcomes.

(05:31): New interventions must be researched first before they can be approved by the Food and Drug Administration (FDA), for commercial availability. That's where a research trial comes in.

(05:43): There are two types of clinical research trials: observation and interventional. Observation is just as the name says, scientists are just going to observe patients and collect subjective data. For example, we're asking you to fill out a questionnaire to see how you feel today, how you feel a week from now, and how you feel a month from now. Here, patients are receiving the standard of care medical interventions, and we just want to know more about the medical treatment that patients are receiving.

(06:17): Interventional is where new treatment is given and investigated. Here, we're looking at either a brand-new treatment or a standard of care treatment for a new indication. For example, we want to give a drug that's already FDA approved for non-Hodgkin lymphoma to somebody with multiple myeloma. Then, we'll collect information on how that treatment affects the patient's cancer. Interventional research is how we are developing new and innovative treatments to prevent, detect, diagnose and treat blood cancer.

(07:01): That leads us to the four phases of clinical research trials. In interventional trials, there are three different phases, Phase 1, 2 and 3. Then, for observational trials, we have the last phase, which is Phase 4. Phases of clinical trials are sequential, and treatments must go through each phase to eventually be approved by the FDA.

(07:22): Each phase is defined by unique characteristics. First, in Phase 1 trials, we enroll a very small number of patients to see if our hypothesis is proven in these trials. Then, in Phase 2 trials, we move on to enrolling more patients to see how effective the treatment works in a small number of patients. Then, in a Phase 3 trial, we see if it's better than the standard of care that's already out on the market right now. Going through each of these first three phases to obtain FDA approval takes approximately 8 to 10 years, which is a considerable amount of time.  

(07:53): Then, the FDA may come back and ask that additional information be collected about the already approved drug, which leads us to our Phase 4 observational trials. A lot of work, time, and effort go into getting one drug approved for commercial use.

(08:10): For our purposes, I'm only going to focus on Phases 1-3, as those are the trials that are most pertinent to you regarding transplant and oncology research. At my program at Northside Hospital, we do not participate in Phase 4 clinical trials because it takes away resources from our interventional trials, but that's not to say that Phase 4 is any less important. They're just not a priority for our patients at Northside Hospital.

(08:43): Prior to a Phase 1 clinical trial, scientists have done extensive work in the laboratory and using animal models to attempt to prove their hypothesis. A drug gets to the first phase of a clinical trial based on those initial results and observations.  

(09:04): Now we're trying to see if we can see those same results in humans. These trials are usually ‘first-in-human’ trials, meaning it's the first time the drug has been administered in humans. The drug is usually in very early investigation as we're still trying to figure out if the hypothesis is true or not.

(09:22): In Phase 1 trials, we're focusing on tolerability and the most effective dose of the treatment for patients. That's why we're looking at only a small population of patients, to find out what this optimal dose is and to prove if our hypothesis is true. We want to see if this new treatment has the same results as what we saw in those early lab studies.

(09:43): Or we may want to test the standard treatment that's already FDA approved for use, and apply it to a new indication. For example, giving a graft-versus-host disease drug before a transplant to see if that could eventually help prevent graft-versus-host disease in the future after transplant.

(10:06): Because these trials are first-in-human, we only enroll a small number of patients at a time to observe subjective and objective data in real time. The subjective data means you are reporting any side effects that you're experiencing after transplant. In the objective data, we're looking at your lab results, like bone marrow biopsies or radiology scans, to assess the results.

(10:37): Usually, only three patients receive this drug at a time. We have to collect those results. We want to have an observation period to see what side effects are occurring, and how the drug affects the patient's blood cancer.

(10:52): If we see good results – if we're seeing that the side effects are not that bad and the drug is tolerable – then another three can enroll at a higher dose, and so on and so forth. We will continue to collect data. If those three patients do well, then we can go to the next dose level.

(11:20): Now, we're moving on to a Phase 2 clinical trial. We've gone through the Phase 1 period, we've seen good results, we've found the tolerated dose for patients. We have less restrictions in Phase 2 trials, so more patients are eligible to enroll in this trial, but we're still looking at less than a hundred patients.

(11:57): The goal of Phase 2 clinical trials is to collect more data, and focus on the drug’s effectiveness. How well does that drug work? Remember Phase 1 was all about how well our patients tolerated this drug. Now, we're looking at effectiveness. How well does the drug work, and what are the side effects? Do the benefits outweigh the risks? Here, we do not have to stagger patients, but we can enroll patients as soon as they volunteer and are eligible for the trial. The whole rationale behind a Phase 2 trial is that we're collecting more data to further confirm that our hypothesis is true.

(12:42): The last phase of interventional trials is Phase 3. Here is where you'll hear the words ‘randomization’ and ‘placebo’. When I was coordinating patients' care on clinical trials, these were scary words to patients, because the patients don't have any control. Your clinical trial team doesn't have any control of the type of treatment that you will get. I'm here to dispel you of those fears.  

(13:07): Phase 3 clinical trials are considered the gold standard of research. It removes bias, meaning that physicians can't just choose their preference. Everybody is randomized on an equal basis. It gives balance to the results, so an even number of patients get assigned to each treatment.  

(13:26): The goal of a Phase 3 clinical trial is to see if this new treatment is better than what's already on the market, or the FDA approved standard of care. We want a large sample size for the results to be significant. Patients are assigned randomly like a flip of a coin to a distinct treatment arm.

(13:45): Most oncology transplant trials do not involve placebo because we cannot risk giving you no treatment at all. Patients can be randomized to either the new experimental treatment or the standard of care medical treatment that is already established.

(14:05): Both treatment arms go through the same exact procedures within the clinical trial – the same exact tests, the same exact observations – to evenly and equally compare outcomes. This allows for better assessment of side effects and overall outcomes.

(14:27): Each type and phase of a clinical trial has a different purpose, but each purpose is trying to get to the same answer. Is our hypothesis proven true or false?

(14:38): Initially, we want to know if humans can tolerate the drug or treatment. Are the side effects risks too great to overcome any potential benefits? That's our Phase 1.

(14:49): Then, we want to know how effective it is at targeting the blood cancer and getting rid of it. Does it come back? Can we extend patients’ overall survival? These are the questions that we're asking in Phase 2.

(15:00): Then, lastly, is it better than what is available now to patients? Can we change the standard of care approach to treating blood cancer? Those are the questions that we want to answer in our Phase 3 clinical trials.

(15:16): This next slide shows the general features of what a clinical trial does.  

(15:25): Let’s discuss what this means for you as a patient, and what the process is that you will go through to receive this new treatment. Your physician will present the clinical trial to you and explain why he or she believes you would be a good candidate for the study. They will go through how the drug is supposed to work and when you will receive it. The research team will follow up with an informed consent document – what we like to call the ‘instruction manual’ of clinical research. This is the document that tells you everything you need to know about the drug – when it's given, the side effects, the procedures and tests that you will go through, who to contact with questions or concerns, what, if any, reimbursements you will receive to compensate you for your time, the confidentiality of your data, and a statement that all of this is completely voluntary.

(16:19): You are given an ample amount of time, days if needed, to make your decision. If you decide to participate, you will then sign the informed consent form with a research staff present.

(16:32): Once that informed consent is signed, you will then enter what is called a screening period. Here, research staff are going to conduct and perform several tests. Some may have already been done for standard of care purposes, to confirm you are eligible to participate in the study. Each clinical trial has a list of criteria that patients must meet and a list they cannot meet. It's the research investigator and staff's responsibility to collect all of the appropriate data and tests to confirm your eligibility.

(17:02): Once confirmed eligible, you will begin to receive the treatment. These are known as your ‘on treatment’ visits. Your research staff will inform you of how often you have to come into the clinic, when you'll have to receive the treatment, and any additional procedures that will need to be done in addition to your standard of care visits.

(17:22): For example, at Northside Hospital, we try to have all our research visits occur on the same day that you're already coming into the clinic for a standard of care visit. We try not to inconvenience you for participating in a research trial.

(17:37): Once treatment is completed, or if we need to take you off the study for any particular reason, you will then move into the follow-up period. These are your ‘off-treatment’ visits. Most of these visits can happen by research staff receiving records from outside facilities or calling you to check on you. This data is collected for survival purposes and to see if you're taking any subsequent cancer treatments.

(18:08): Now, let’s address the ‘How’ questions regarding the clinical trials process. How are clinical trials different from standard medical treatment? How are clinical trials reviewed and deemed appropriate for patient participation? How are patients selected and evaluated to participate in a clinical trial? How are patients monitored and evaluated during their participation in a clinical trial? How are clinical trials funded?

(18:40): Here is the comparison between clinical trials and standard medical treatment. Clinical trials are considered experimental as the drug we are testing is not yet FDA approved. We're testing the medication to find out those results. Standard medical treatment is already established and FDA approved for use in that particular indication, i.e. results that are already proven and tested several times over for the standard medical treatment.

(19:13): For clinical trials, patients volunteer to participate to receive this treatment and give their informed consent for that participation. Physicians give patients options for their specific conditions, which could include a clinical trial.

(19:28): If you decide to follow the standard of care route, your physician is going to choose the best course of action for you. Whatever type of treatment he or she feels is best for you.

(19:36): For clinical trials, if you choose to participate, you will receive the protocol treatment, and you will need to abide by those guidelines and those rules.

(19:47): The most important part to remember is that all medical treatment, and all supportive care measures – such as treating nausea and vomiting after transplant – all came about because of clinical trials.  

(19:59): Clinical trials and the questions they answer help establish standard of care treatments, algorithms, and procedures for transplant in blood cancer.

(20:13): In this graphic, I've split out the different types of clinical trials based on the types of treatment that they give. There are chemotherapy trials where we're testing new drugs to help kill cancer cells. Patients will either be newly diagnosed – meaning they just found out that they have this particular blood cancer and now we want to give them this chemotherapy to kill those blood cancer cells – or their disease has come back or is not responding to that initial treatment.

(20:54): For transplants, examples of clinical trials we are looking at include new graft-versus-host disease treatment or preventing graft-versus-host disease, or looking at a new conditioning regimen for the chemotherapy you receive prior to transplant. Maybe there's something new that we can add into this regimen that will help prevent your disease from coming back, or give you better outcomes, or reduce some of the side effects that you could experience after transplant.

(21:24): Another example is giving a standard medication earlier to prevent infection. For example, instead of starting an antibacterial medication on day plus five after your transplant, we're giving it to you on day minus one right before your transplant to see if we can help prevent that infection from coming about.

(21:45): Our last type of clinical trial is focusing on one of the newer developed treatments at the moment. These are our immune effector cell therapies, where we're taking your immune cells and regenerating them to help them recognize your individual cancer cells and kill them. Or we are taking a healthy donor's immune cells that can recognize your particular blood cancer cells and kill off those cells.

(22:23): It's also important to note that by participating in a clinical trial, one of the differences compared to standard of care medical treatment is that your evaluation while under a clinical trial is probably going to be a little bit more frequent, and maybe a little bit more thorough than what we would do for standard medical treatment. That's because for standard medical treatments, we have proven results, and we know what to expect with this particular treatment.

(22:55): We're still trying to answer those questions with clinical trials studying medications. That's why we're asking patients to come in more frequently to the clinic and stay a little longer. We want to make sure all potential side effects are observed and taken care of, and ensure our patients are safe and okay after those medications are given.

(23:22): A lot goes into how clinical trials are reviewed and deemed appropriate for patient participation. Initially, before the trial even reaches Phase 1, there is a lot of background review. There is a lot of animal testing and a lot of testing in the lab. This is how we develop that scientific question – our hypothesis – that we're trying to answer. We're getting the scientific results and all of these protocols for clinical trials are designed by experts in the field. These are not just some scientists that are thinking up a question. They have experience in the hematology, oncology, and transplant world and are genuinely trying to figure out the answer to a question that will help improve patient outcomes.

(24:21): Clinical trials also go through extensive scientific reviews. Even to get to a Phase 1 clinical trial, you need FDA approval. The FDA must give you the ‘okay to proceed’ to get the clinical trial off the ground. The FDA will be looking at all those lab-based results that happened before the trial was ever introduced to humans to ensure that the trial is safe for human participation.

(24:54): While the trial is going on, there are several committees that review the data and the results on an ongoing basis. You have your oversight committees and your steering committees. They're reviewing the data constantly. They're having meetings weekly, bi-weekly, and monthly, to ensure that everybody is aware of the data, and everyone is aware of the results. They can either move forward with the next dose in a Phase 1 trial or they can continue with the trial in Phase 2 or Phase 3.

(25:26): Lastly, you have your ethics review. This is all about human subject protection, making sure that human subjects who are participating in a clinical trial are protected. Not just protecting their data and confidentiality, but also ensuring that the risks of the trial do not outweigh the benefits, and that there will be some benefit to patients in participating in this trial. Your institutional review board does that. For a clinical trial to be approved at a certain center, Northside Hospital for example, you have to have an institutional review board review and approve the trial to be conducted at that particular site.

(26:14): The physician must consider many factors before patients are selected and evaluated for a clinical trial. Your physician is the one who is reviewing your records up front. We're looking at your basic eligibility criteria here. Do you have the correct blood cancer diagnosis for this clinical trial? Did you receive the appropriate amount of treatment? How are your lab values? We're looking at these basic criteria before we even discuss the clinical trial with you as a participant.

(26:50): If you do meet these basic eligibility criteria, your physician is going to talk to you about the clinical trial, giving you all of that upfront information about when the drug is given, what the drug is supposed to do, what are the potential side effects of the drug, etc. That way you are completely informed about the trial and about the drug so you can make your decision.

(27:17): If you do decide to participate, you sign that informed consent and go through that screening process. That's where all your labs are done. We conduct a physical exam including any required procedures such as a bone marrow biopsy or any scans that are required.  

(27:35): The clinical trial lists out several specific criteria that patients either need to meet or not meet, and it's all based on your history –such as the type of treatment that you have received previously. It considers whether you have a history of any medical conditions like a heart attack, a stroke, or history of hypertension. We're going to be looking through your history in-depth to confirm whether you are eligible or not.

(28:18): Once you have been deemed eligible to participate in a trial, you are extensively monitored while you are participating in a clinical trial. We have all kinds of people reviewing everything that is going on with this clinical trial. We'll start first with the physician review. Every time that you come into the clinic, whether it is for the clinical trial research visit or for your standard of care visit, we are looking at your lab results. We are reviewing all the side effects that you're reporting to us. Your study team is asking you questions. Your regular nurses are asking you questions. We just want to make sure that your safety is a priority here.

(29:06): We also have a third-party review, and an oversight committee that comes in. This is where an external committee is reviewing all the data. It's important to have these types of committees because they are impartial – they don't know you or the clinical research team – they are purely looking at the data to see how patients are responding to this treatment.

(29:33): We also have the study sponsor for review. Study sponsors review all the data in our database.

(29:40): We also have that ethics review, reviewing any unexpected events and making sure that informed consent is comprehensive.

(29:50): There are many ways in which clinical trials are funded. You can have industry sponsors such as pharmaceutical companies like Bristol Myers Squibb, Johnson & Johnson, or Sanofi. They are the ones developing clinical trials and asking sites to participate.

(30:11): There are also government-sponsored trials, like the National Institute of Health or National Cancer Institute sponsored trials.  

(30:19): There are also investigator-initiated trials. It's very possible that the clinical research team, or your physician, has developed this protocol on their own. They want to know the answer to a question regarding their patient population.

(30:39): Why are clinical trials stopped early, why do clinical trials use placebo, and why should you participate in a clinical trial?

(30:49): It’s possible that clinical trials are stopped early for several reasons, and I'm going to highlight three of them. It's possible that side effects are much more prevalent than what we have seen in lab studies. We're constantly reviewing the risk versus benefit analysis. Are the risks outweighing the benefits or vice versa? We want to make sure that the benefits outweigh the risks. These treatments may have too much toxicity, resulting in patients needing to come off the trial and the clinical trial needing to stop.

(31:30): It's also possible that clinical trials have stopped early because we're seeing really great results. We're already proving that it's better than routine care and we can fast track this treatment to FDA approval.

(31:46): Lastly, it could be a sponsor’s decision. I will say for Northside Hospital, we've recently had to close some clinical trials because the sponsor has decided to reprioritize their resources, and they can no longer fund this particular trial.

(32:00): It's also possible that there's slow enrollment, that we are just not finding the right patients for this clinical research study.

(32:11): Clinical trials use placebo to help reduce bias. Phase 3 clinical trials are your gold standard for clinical research. We're randomizing patients because we want to reduce the bias, and basically flipping a coin to see which treatment that you will receive.

(32:30): There are blinded and unblinded clinical trials. Blinded means we are unaware of the treatment you are getting, and unblinded means that we do know the treatment you will be receiving. Taking away our choice of treatment you are going to get, reduces bias. There's a cause-and-effect relationship within the clinical trial as well. If we can prove that there might be a relationship between a new treatment and its outcome, it leads to more reliable evidence for clinical decision-making about the treatment your physician wants to give you.

(33:04): Having received all this information, why should you participate in a clinical trial? You are still going to receive expert medical care no matter what decision you make, whether it is to participate in a clinical trial or if it is to receive standard medical care.  

(33:26): The unique thing about a clinical trial is that you're going to gain access to the latest treatments and techniques. That new immune effector cell treatment is in the clinical research world right now, and you’d be able to access those latest treatments by participating in a clinical trial.

(33:49): A significant motivation for a lot of patients is being able to contribute to medical advancement and helping future patients.  

(34:07): There are some factors to consider when you participate in a clinical trial. Your time commitment could be a little longer. You might be required to come into the clinic a bit more frequently than what would be required for standard medical treatment. You might have to go through some additional tests or procedures for a clinical research trial.

(34:29): It's also possible for you to consider a second opinion. If this is the only option that we are able to offer you, you can always look somewhere else. Look at a different center to see what other options are available to you.

(34:43): Just as a reminder, sponsors are trying to offset costs for patients. They're trying to do a better job of this now, like reimbursing you for parking, meals, and mileage. Coming to the clinic every day and paying $10 for parking adds up. I have seen that sponsors are trying to help patients in that way.

(35:11): Finally, let’s address our ‘Where’ questions regarding clinical trials. Where can you find out the results of a clinical trial and where can you find out more information about a clinical trial?

(35:27): Results of a clinical trial are usually available on clinicaltrials.gov. However, they are not available on that website until after the study is completely done. This means all patients have participated, they have completed their follow-up, and everything is said and done. Because of this, it's very possible it will take 8+ years for these results to become available.

(35:56): Sometimes sponsors provide information to the clinical research teams for them to disseminate to patients. It's also possible that your study physician can give you that information as well.

(36:09): If you would like to learn more about clinical trials, here are some websites you can visit. At clinicaltrials.gov, you can type in certain words and see which clinical trials pop up. The Leukemia and Lymphoma Society has a list of clinical trials as well.

(36:29): You can also visit your local hospital, university, or clinic websites, and social media. A lot of clinical trials teams are posting on social media to promote the clinical trials that are available at their centers.

(36:52): If you are considering participating in a clinical trial, here are some useful questions to ask your clinical team, your physician, your nurse aide, and your coordinators. What is being researched and how is the treatment given? How long do you have to stay in that clinic in order to receive the treatment? Will you need to make extra trips in order to see your doctor? Do you have to pay for any part of the trial? Will your insurance cover treatment? If you participate in the trial, will you be able to see your own doctor? Can you change your mind and withdraw from the trial at any time? What happens if the treatment doesn't work for you or what if you have any bad side effects? What happens to your medical care when the trial is over or finished?

(37:36): These are some questions to keep in mind if you're considering a research trial, and I would be happy to take any questions at this time.  

Question and Answer.

(37:46): [Susan Stewart]: Thank you very much, Ms. Guzowski. That was a great presentation. Very comprehensive.

(38:07): The first question is, I'm definitely interested in participating in a clinical trial when my multiple myeloma relapses. How do I go about researching what's available to get into a database for people interested now, so that I can avoid delays when the disease relapses and becomes refractory to my current line of treatment?

(38:33): [Caitlin Guzowski]: I would look at your local university or your local hospital to see if they have any clinical trials available. Another way you can go about this is if you go to clinicaltrials.gov and you type in ‘multiple myeloma’ into the search box, you can filter for the clinical trials that are only participating in your state. That will at least narrow it down. Also, on clinicaltrials.gov, they give you a list of contacts at particular sites. You can email the study physician directly to say, "Hi, I'm interested in this clinical trial when my disease relapses. I really want to get in your queue when this trial would be an option for me."

(39:21): [Susan Stewart]: That is true, clinicaltrials.gov does have a lot of information. I do know, however, that a lot of patients find it very difficult to use. I would suggest reaching out to the Leukemia and Lymphoma Society, which has patient navigators to help you locate clinical trials. They're able to translate a lot of that very complex information you see on clinicaltrials.gov into a more easily understood language and help you sort out which trials might be worth pursuing. I would definitely give Leukemia and Lymphoma Society a call or email them for help on that.

(39:59): Does insurance cover clinical trials, and what happens if they don't?

(40:08): [Caitlin Guzowski]: It does really depend on your insurance if they cover clinical trials or not. That's something that, at Northside Hospital, we're very fortunate to have an oncology business office that does a lot of that leg work for us. If your insurance does not cover clinical trials for Northside Hospital, we are able to provide financial assistance to patients so that they can participate in a clinical trial.

(40:36): It's very possible that the insurance won't cover certain procedures that are in that clinical trial. If that's the case, we have always gone back to the study sponsor, like the pharmaceutical company who's funding the trial, and ask them to cover those specific procedures for a patient to participate. They're usually very amenable to that.

(40:57): [Susan Stewart]: What happens if the drug being tested in a clinical trial is actually less effective than standard therapy?

(41:10): [Caitlin Guzowski]: If we see that in a Phase 3 trial, then the study treatment and research is stopped at that time. If we cannot prove that there is a benefit to receiving this treatment over what is already approved, that clinical trial stops, the research on that treatment is done, and it doesn't go to the FDA to get approval.

(41:36): [Susan Stewart]: Are all the drugs that are used during transplant in CAR T-cell therapy FDA approved? If not, why?

(42:15): [Caitlin Guzowski]: All drugs that are used in transplant in CAR T-cell therapy have an FDA approved label. It is possible for physicians to use them off-label, for example, giving it earlier in the transplant process than what is standardly approved. I don't have a great answer for how physicians are able to do that without having that FDA approval.  

(43:04): [Susan Stewart]: Can I enroll in a clinical trial if I'm not currently at a transplant or CAR T center? Can my local doctor enroll me in a clinical trial?

(43:19): [Caitlin Guzowski]: Your local doctor would have to be participating in that clinical trial, and that center would need to be a site participating in that trial. However, it's possible that your local doctor might be a part of a larger network. For example, Northside Hospital has several community oncologists that work underneath the big umbrella of Northside Hospital, and those local oncologists can enroll patients in a clinical trial because they are affiliated with Northside Hospital.

(43:56): I don't know how that works with your local oncologists. If your local oncologist is not part of a bigger network that has access to clinical research trials, I would suggest asking your local physician about being referred to a center that does have clinical trials, and specifically the ones that you're looking for.

(44:20): [Susan Stewart]: Why is there not more collaboration in clinical trials with different medical institutions? There are so many trials limited to geographical areas that are inaccessible to many people who would qualify. It would be great to have the trial available across the country in various areas so more people could participate.

(44:46): [Caitlin Guzowski]: I completely agree with you. I do know that pharmaceutical companies are limited in the number of sites that they can have participating in a research study. That's purely due to funding. How many sites can they pay to run this clinical trial? There may be some bias for the bigger institutions like MD Andersons and City of Hope. I know that it is difficult for patients who don't live near those big centers to participate in clinical trials.

(45:29): I do believe that now – and probably the past couple of years – there has been more of an effort to get clinical trials into areas where there isn't a major institution so that more patients can have access. I think it's still a work in progress and it's something that will continue to need to be worked on. It's not something that's going to happen overnight. It's going to take years for that to happen. But I do know that they are trying to work on it.

(46:06): [Susan Stewart]: How much more time does a clinical trial typically take for a patient as compared to standard therapy? I think they're trying to assess how much extra time they need to build into their schedule.

(46:27): [Caitlin Guzowski]: It really depends– I don't know if I can give you an average amount of time. For a particular day, if we're just talking about a 24-hour period when you're going to clinic, it's very possible that your standard medical treatment might only be a 4-hour visit. But for a clinical research trial, we might be talking upwards of 6 to 8 hours, just because the clinical trial might mandate that we collect samples for 6 hours after you get the research drug, because we're trying to see how that research drug is working in your system. Is it still active 2 hours later? Is it still active 4 hours later? Is it still active 6 hours later? It really depends on the clinical trial and what's mandated in the clinical trial.

(47:19): From my experience, looking in general at clinical trials versus standard medical treatment, I believe that you come to clinic a little bit more often. If we're talking about a cycle which is 28 days, I would say you're probably in clinic 3 to 4 extra days a month during that cycle than you would be for standard medical treatment. That's purely for observational purposes. We obviously want to make sure that you're okay. If you're experiencing any side effects from the research drug, we want to know about it. We want to take care of you. We want to record that information so that we can send it to the sponsor.

(48:01): [Susan Stewart]: Can I drop out of a clinical trial if I change my mind or if I have some bad side effects?

(48:19): [Caitlin Guzowski]: Yes, of course. Research is always optional, so yes, you can. It's voluntary to participate at the beginning, and even if you do start participating and you don't like the side effects, or you don't like that you're coming to clinic an extra 3 to 4 days a month, you have the option to withdraw your consent at any time throughout that entire process.

(48:42): [Susan Stewart]: Closing. Great. Good to know. Well, with that note, I think we'll end the workshop. On behalf of BMT InfoNet and our partners, I'd like to thank Caitlin for breaking down clinical trials and explaining their importance. Thank you to the audience for your excellent questions. Please contact BMT InfoNet if we can help you in any way and enjoy the rest of the symposium. Have a great day.