Hello everyone, welcome to our webinar, Finding the right dose using patient data in the early phase before clinical trials. We are happy, that you are here today. This is really very exciting in this very exciting and very interesting discussion. You can hear the interpretation on Zoom and for this please follow the instructions you see here. You can click here on this globe click, then you can choose your language and the webinar will be in English and You can then mute the original audio and you will only hear the webinar in your language, i.e. the language you have selected. And so we have that Interpretation in the languages listed here. We also have a number of terms with you shared, which you may hear during the webinar. We would like to be with ours Sponsors and partners thank you for the IASLC program this year. And the goal of this IASLC program is to help active lung cancer patients for speakers to support the PRAs. And the objective is to build a support network for the LCPRAs, to educate about lung cancer science and research, to model effective avenues for communication, science and research and also identifying opportunities for research funding. We have a few more housekeeping notes here. Feel free to submit questions. We will use the Question and Answer window to do this. The questions will then be answered by the speakers at the end of the session Discussion participants and you can of course also view the reference material and see the instructions regarding interpretation. The chat is not for the participants activated so that they can communicate with each other. So please use it the Q&A box. This webinar will be recorded and will be posted again later in the relevant Languages provided for you to review later. We have four speakers and a moderator who can share their knowledge with you. Miss Dr. Melinda King-Kalimannis, she is the director of patient-focused research and Melinda worked at FDR, at the Center of Excellence. Then we have a recording of Ann Leiser. She was diagnosed with early-stage breast cancer when she was 18 years old. She is a patient leader spokesperson, she is an author and she has the Patient Center, the PCDI, the patient-centered initiative Dosing establishes and supports patient information to account for unique characteristics and find the optimal dosage for patients. Our third speaker is Lee Jones. Lee Jones is a colon cancer neurologist, he is a supporter of patient research, his initiatives. He has different Boards with different research papers, he speaks at conferences, he is the co-author from various publications and patient research advocates. Then Janice Cowden is with us. She will also participate in the question and answer session. She has stage 4 negative breast cancer and she is an active member of PCDI, the Patient Centered Dosing Initiative and so Janet will be moderating the question session and she is an engineer and she is an advocate in the area of cancer research. And these experts bring different perspectives to this discussion Together they will give us a comprehensive overview to find the optimal dosage to understand better. So let's start right away and give the floor to our experts, our speakers. OK. I would like to share my screen here again. OK. So, thank you very much, Sarah, for this nice introduction and of course also many thanks to the IASLC program, that I was invited to speak here today. I have a little overview here of what we're going to talk about. So let's start with how we normally do it Dose for cancer treatment is determined. This is usually done in the early stages of clinical trials. We will talk about the regulations and how the dosage there in the era of targeted therapies. After that we will talk about the potential impact patients may experience when optimizing the Dose. And then we'll talk about the role they can play in this discussion. And then Ann Leiser will speak. She is the founder of the initiative for patient-centered dosing. And Lee Jones will then share his perspective with us here. And he also took part in various conversations and discussions about dosage. And finally we have the question and answer session with Lee and Ann and Janice. So I have a list of the terms here. We also put that in the chat. And the So link is always available. Then you simply have a reference to the terminology. But there are some points you should focus on, which is what this conversation is about will go and which will appear again and again. This is the dose-limiting toxicity. Describes side effects of treatment that are serious enough to prevent increasing the dose of this treatment. There is a time window in which this is observed. And everything is examined before the study begins. Then we have the maximum tolerated dose, the highest dose of a drug that meets the desired Effect achieved without causing unacceptable side effects. Then we have the patients Experience data. This term was introduced in the USA before legislation. But that relates refers to the data that is collected and that provides information about the experience of patients suffering from an illness and the effects of the illness can have on the therapy. But it can also be a matter of patient preferences act in relation to treatment. And the usual data, which is the patient reported results. This is a survey. The patients are asked directly about this their condition. And so these answers are not checked by the clinicians. So before we get started, I would like to give you a little bit of an overview what happens. So here on the left side we see what happens before we start with the Test phase on humans begins. To help you better understand how the medication works, We usually test this on animals to establish the safety profile. Then we go here, then we enter the clinical study phase, the clinical trial phase. And these trials, these studies are going into phase 3. This is where the treatment comes on the market. And in Phase 4 there are certain activities that are undertaken to demonstrate that the drug is safe. But today we will focus primarily on Phase 1, with the transition to Phase 2. The traditional study paradigm at Cancer drugs, that is the 3 plus 3 design. And all the parts that we see here are so predefined before the study even starts. And this is all set out in the study protocol, So here we have the three green dots, which represent three people who are taking part in the study. And down here we have the timeline and on the side we have the dose being increased. The that is, these three people seen below start with the lowest dose. And you So you can see that no one there experienced dose-limiting toxicity. That would therefore prevent this treatment from being given. And then there is a higher dose, three people there again, it's exactly the same, no toxicity. And that doesn't mean that there were no side effects at all, but the dose that arises there, are not so strong as to cause toxicity. And then we go to the next one Phase and let's say that's 15 milligrams. Here we now have 15 milligrams and one person out of these three experiences this dose limiting toxicity. And what happens so now? So there are three more people who are given 15 milligrams, to see what happens. Here we see that no one experiences dose-limiting toxicity and we move on to the next dose, again with three people, let's say 16 milligrams. And now we see that two people experience this dose limiting toxicity and then let's go back again. And that will be the recommended dose for the next study. And that is the RP2D, which is the recommended dose for the second phase. And here we have another picture. So here we see this cycle. So you can always, So it goes in a cycle until you get here again, until you get to the tolerated dose. So why are we even considering changing the paradigm of dose selection, so what I just described is based on us finding the maximum tolerated dose find. And yes, with respect, these days we are more concerned with studies for targeted therapies. And we have a lot of evidence that shows that the maximum The tolerated dose is not always the same. For example, there is no maximum tolerated Dose that was found. So if we start the preliminary studies with a non-optimal dose, then we have the highest chance of success with the study. And another thought is, with the targeted therapies, which are usually administered over a longer period of time, than conventional chemotherapy, for example six cycles. But now, if we take, for example, people who suffer from lung cancer, so they don't stick to treatment, until the disease worsens. So we have to see how we change the dose finding. And that's outside the scope of dose determination. And of course there are also those who are not compatible Side effects. And of course these are an opportunity that is not taken advantage of, a missed opportunity Chance. And what is also important is that there are irreversible side effects that then Limit subsequent therapy options for these patients. So, I want to here provide a brief overview of this dose. Over the decades, in the late 80s and early 1980s In the 1990s, when HIV medications came onto the market, people had exactly the same conversation about dosage as they do now. And there was a paper about it and it showed that generous doses of 300 milligrams, one has seen that a dose of 300 milligrams which had similar clinical effect, with fewer safety issues. And so you have seen that this was the lowest effective dose. And then now we come to the year 2000. And someone asked a question about changing one dose after the drug is approved. So this paper deals with FDR and the co-authors. And it always works here nor about chemotherapy and the dosage of oncological medications. So this has been observed for a while. And in 2015, the JPMA, which is a Japanese regulator, has published a guide that outlines dosage considerations for the Japanese Population contains, in this context, i.e. in the context of clinical studies. In 2019 there is one The initiative was given by the CADTH. But this year the Canadian agency has a guide published on the dosage and when to take it. And now it's getting a little faster. In 2021, the FDA spearheaded a dose optimization project. In 2022, EMMA established the Cancer Drugs Forum. And this year the FDA a guide published for industry on dose optimization in cancer clinical trials. Let’s talk a little more about the Oncology Center of Excellence. And the goal is really, to work together and educate schools. Patients really want dose optimization to find those that maximize the treatment, the efficiency of the treatment and the Safety of treatment. And here we see, so here guides have been published and it will also be a final version of it. There are workshops and other public events. The FDA will also offer developers the opportunity to discuss these optimizations with them. And of course the hope is to develop new strategies to use non-clinical and clinical data and to take into account the use of a range of doses. So not only that recommended dose, for example that 15 milligrams that we talked about earlier, But maybe you take 30 to 15 and look at this range and see how it works in the next phase of your studies. There are still a few points that I need to address, particularly with regard to the guide published this year became. We're talking about the maximum tolerated dose and the FDA has said that that's a dosage that may not be well tolerated. And we have seen that there is a negative influences what people feel and how they behave and how they function. We I'll get into that a little later. So he took part in that early discussion, to provide treatment. Then there are the patient report results and there is a systematic way how to find a dose and how to record the side effects, in order to understand how treatment can be tolerated better and thus the patients as well stay with treatment. And the last point is the involvement of patients and that Patients need to be included in order to be important considerations To provide safety and tolerability for dose optimization. Let's take a look the patient outcomes, the patient outcomes and the FDA has that as an important concept considered. So here we see, here we have a series of questions and there are different ones Symptoms and side effects that may occur within the drug development program and we picked out a few there. And the selection of questions is based on similar drugs, for example you can get the information from the State Cancer Institute use and here for example I have a question, an example of a question, that is of patient outcomes. So here we see, that doesn't mean that there are no other concepts which are also interesting, but the regulators are very interested in i.e. how closely these side effects are related to the medication. And this information is therefore considered trustworthy by FDR. I have an example of one of those here Questions. Here, for example, are there problems or one, or that doesn't mean other things are not important, but they are adapted to the respective situation, for example the symptoms the disease, how relevant they are and depending on the disease and the course of the disease, For example, with lung cancer or breast cancer, there are of course differences. And also in Which phase of treatment you are in, is this an initial treatment or is this a further one? Treatment after a previous treatment did not work. So what is the benefit included? You are the experts, so you are the experts, how you feel, how you function, how everything is going. And these numbers that we see here, so here we see the gray line is for the fatigue and then what the patient said about it with the timeline here and that Incidence on the left side. So we see here that there is a difference there. I believe, the doctor probably asked on a scale of 1 to 10, but for example here is this Fatigue. And as already said, here we have a systematic side effect. So it won't just asked that someone should report their side effects, report on them, but it asks about a series of side effects and always at the same time done so that you can really see the progression over time. This is especially important when we look at the less difficult, serious side effects. Of course you can have an impact and knowing about it can help to better design the experimental phases. For example in phase 2 or 3 we see, that diarrhea does not occur in the first few months, but rather in the fifth or sixth month the treatment. And it might be good if, in the third phase, you could, for example, use antidiarrheal Introduce medication in order to anticipate exactly these side effects in advance. And that is also an important consideration. I think that's very important in the response on medications or when we see the differences in challenges. here we see the doctor's report. Normally these are the criteria. This is the most important criterion when it comes to Diarö, for example. So we see number 1 is not strong or not heavy up to 4 and then up to grade 5. And then below that we have the patient's report. And what What you can immediately see here is that there are other options that we don't have for doctors. And if we look at these different categories and when we create a map from them, So there are no serious side effects here in terms of the regulations. But we see an increase from 4 to 6. But I would imagine that people here consider this to be more common will report because this creates a great dependency on the toilet. So it's not one Surprise how it is rated here and how this rating is arrived at. And the FDA has explains that patient and physician reports do not need to be reconciled. If you So you have a discussion and if you have a certain level of rejection there, then you can use this document. So what role can you play in this discussion? It is very important that those involved and that means the regulatory authorities, the doctors, that they are over clarify the value of this approach. So you can get involved there as a consultant engage. You can talk to the stakeholders. This can be organized by professional societies, by government associations or by patient representatives. It also gives us the opportunity to participate in the Institutional Review Board and to review study documents. And there are always, in these committees there are also always laypeople. Universities also have committees and WCG is also an independent entity in the UNITED STATES. And here we see, here you can find out more about what working in the IERB looks like. And with that I come to the end. Thank you very much. Welcome. I am Anne Leiser and on behalf of the Patient-Center Dosing Initiative or PCDI I would like to thank the IASLC for the invitation, to present this overview of our work and our key findings. For background, the PCDI was used four years ago by patients with metastatic breast cancer brought to life. Our aim was to reduce the frequency and severity of treatment-related adverse events in MBC patients. We have quick formed an advisory board of medical oncologists to ensure that everything we did was medically and ethically sound. We have the root cause for that Researched treatment-related toxicity and found that it was mainly due to the use of the maximum tolerated dose or MTD as the recommended starting dose or RSD is due to cancer drugs. We also found studies in which the lower doses and some drugs were as effective as the MTD and involved less toxicity brought. Our conclusion was therefore twofold. If possible, the MTD should be changed become. More is better. So change this paradigm and there should also be conversations between Doctors and patients are informed about the best dose for the patient at the beginning and after completion of treatment Patients are supported based on the patient's individual characteristics. We conducted two surveys. We have a survey for patients with MBC in 2020 guided. The following year we conducted a survey of medical oncologists who were treating patients with Treat MBC. But the goal of the survey was the same. We aimed to assess the prevalence and severity of adverse events associated with MBC treatment understand the patient. We wanted to find out what level of communication between doctors and patient about side effects takes place. We also wanted to find out how... low doses affect quality of life and the effectiveness of treatment. And finally, we wanted to determine to what extent patients and doctors are willing shared flexible dosage options based on the individual's personal characteristics Discuss patients. Essentially we wanted to find out if we were on the right track were. We received 1221 responses from patients and 119 responses from oncologists. The Oncologist responses are shown in gold and patient outcomes are shown in white. The vast majority of patients, 86 percent, arrived, at least one bad one to have experienced treatment-related side effects and the majority of oncologists underestimated them. For them, that number was 60 percent or less. One in five patients had side effects as a result, go to the emergency room or a hospital and the oncologists' estimate was 15 percent or less. More than two out of five patients required one or more treatments let it be phased out and the oncologists' estimate was 37 percent. Plus all patients, so 98 percent, informed their doctors about the side effects and of the patients who had one When the dose was reduced, 83 percent felt better with a lower dose. 71 percent of Doctors reported that patients felt better with a lower dose and that the Efficacy similarity was as for RSV dose. We also asked patients and doctors whether they believe that a higher dose is always more effective than a low dose and more than half of patients and 85 percent of oncologists do not believe that the MTD paradigm, So more is better, really works. And finally we asked the groups if they would be truly willing to provide flexible dosing options based on patient characteristics to discuss and more than 90 percent of both groups said they would be willing to to do that. So these results supported our mission. It was determined, that there is in fact a significant prevalence and severity of side effects and most Patients with side effects and that patients feel better with a low dose and that they are able or willing to guide on dosing options depending on individual characteristics. There is one more thing we did in the survey have carried out, but there is something different when it comes to the results. And in 2021 we had the privilege of presenting the results of this patient survey at the global meeting to the American Society of Clinical Oncology. And since then we have presented our results in various posts and also in the respective magazines. And five months after our talk at ASCO, the FDA announced the following. Our patients have said loud and clear that the drugs are too toxic. The Patients deserve a better tolerated dose. And we really liked that. And I would like to draw your attention to the fact that there is a defense from the paradigm anymore is better with NTD there. For experimental drugs, particularly in Phase 1, the FDA's Project Optimist encourages industry to use at least two doses on the on the basis of effectiveness and tolerability and not instead of automatically choosing the maximum tolerated dose. Regarding approved drugs on the market, As part of the FDA's Project Renewal, the dosage of certain approved cancer drugs is being reviewed. The oral chemotherapy drug Solota is the first Drug receiving a dose-related label update under this program and in the clinic, PCDI continues to encourage physician-patient discussions about flexible dosing. And that will also be important in the future, because the current... Approved medicines currently on the market continue to be based primarily on this prescribed to the MTD. And it will take time for drug development to put Project Optimist's new paradigm into action. The reaction of the patients in the actual world may differ from clinical trial participants and us are simply unique individuals and everyone needs something different. The most important insights into initiating change that we gained along the way It should be said that patients and professionals should always be included in the team if possible. Investigate, get to the root of the problem and evaluate the solution concepts. Make sure all team members recognize that the only bad idea is the one that is not communicated. Develop one together Mission, an order and a plan with strategies so that you can then test them. And the data speaks for itself. If you can do studies and I know that you can There are certain confounding factors like AI, but you can, if you can do a study, they should Results are evaluated and then published, if possible. If necessary, re-evaluate and edit. And the path to success is apparently easier, but there is a lot of work behind it. This includes motivation, ability and perseverance. And finally, I would like to share a few important findings about the study with you. The first is to avoid open-ended questions that require the candidate to fill in the blanks must. This creates significant problems with data cleaning and quantification. After the survey questions have been developed, you should conduct a pilot study to gather feedback from a group of potential recipients. Plan how and where the study is advertised, in which language and by whom. We have also developed flyers in Spanish and English. Engage an IRB or review board before you start the study. This will give you more credibility. Distribute during After the study, a quota table is provided to determine whether you need to advertise additionally to attract more participants. Our speed graph is here in white and at a low point we created this infographic on the right, in order to attract more participants. And finally, disseminate the results, present and publish the results wherever you can, both informal and professional. And last but not least, I would like to thank you for your attention thank you. Thank you. We're hearing from Lee Jones now. Thank you, Sarah. I would like to thank IASLC and STARS for participating in this webinar. The cancer patients are key factors in my life and in my career. I talk about my experiences and ask other advocates to to get more involved, especially in research, because we all know as patients we need as much help as possible. I report two conflicts of interest due to the Payment I receive for Patient Engagement Councils from Bayer and Genmark. You pay me to do this work and help patients at the same time. Regarding the topic the webinar, how did I get involved in this issue and give a little context, how you can similarly improve your work by looking for opportunities. Participation at STARS is a good start. I had the opportunity to take part in a training course ten years ago. We spent two and a half days there with oncologists, radiologists and others talked about the topic of cancer. We knew very little back then. Today we know more, but that was a good start. In lung cancer, things move very quickly and faster than in other types of cancer. So it's an interesting opportunity. Something that comes out The training revealed that we had no plan on how to proceed. That was for some difficult, but also positive because we were able to follow our own interests in advocacy. I decided to meet people at my maintain clinic. At that time I was involved in three IRBs. Like the speakers said it's a great opportunity. As an IRB you have the opportunity to create protocols for clinical See studies. This gives you an idea of what is going on in cancer research. And you learn a lot in terms of understanding what goes on in cancer research. What's a good one Protocol, what a bad one or more importantly? What is a good consent form? Man You almost have to be a doctor to understand this. But we have the opportunity to correct that, when we check these. I made important suggestions that were incorporated into the feedback for the study sponsors. This is really important work. 2018 has ASCO invited me to be an advocate for a panel of experts working on the ASCO policy have worked for phase 3 cancer patients. This emerged from a clinical study, which showed that for phase 3 cancer patients, three months of chemo treatment was just as effective were like six months of the same drug and obviously with less toxicity. And That was interesting for me because I received that myself in my treatment. As a patient in stage 4 I did not have the benefit of reduced doses. But what came to mind was how many people have we poisoned over the years. And I was treated 20 years ago and unnecessarily so, because they had to pass it through. These are peripheral nephropathies, these are side effects that patients report. That same year I was diagnosed with cancer Research invited and that's a name I remember as I work with them a lot have worked together. Regarding the issue of tolerability in cancer studies. This definition has always been clinically oriented. If the doctor says you can tolerate it, then you can tolerate it. So it's based on plaque counts, liver function, those kinds of things. But they don't actually ask the patient how they feel. And the Patient representatives in this group, I mentioned this concept. Why are we closing? do not take the patient perspective into account when we talk about tolerability. Because the patients also have the right to say, I don't want this anymore. I no longer want this medication. And that is the final definition. That includes significant change. The tolerability of a product is the degree to which the product's ability to avoid side effects or concern the patient's wishes as to whether they need to continue therapy. Tolerability should take into account the patient's direct opinion while receiving treatment become. And as you would expect, this direct measurement, results are from Patients are reported. So that's how I got involved in tolerance and results. And this is also a good opportunity for other advocates. In forensiccancerresearch.org, find articles and other white papers. And you also have videos of many of the sessions that you do. We have also started a new group of advocates to invite. This gives you the opportunity to become a member of these interest groups. The FDR, drug manufacturers, research institutes and many experts take part there. The can be a little impressive at first. But as you have heard so often, we are the experts in our illness and you, the other experts, don't know a lot. Other people I've worked with have said in terms of compatibility, I have a lot of Learned from you and that we have to take the patient perspective into account. I have on that at the same meeting as FDR and more is not always better. The FDR representative spoke about dose optimization and I about tolerability. Together we have conveyed a good approach can. In 2022 there will be another group, Friends Work together. And they're called PROS for informed compatibility. And part of the Tolerability is the patient experience measured via PROS. And we have first Studies, phase 1 and phase 2, discussed. The decision was that it could be done and that it would be positive. But there were many other problems that brought me to the group, where I am now. And Belinda is also in the same working group with me. She are investigating initial studies on dose determination for patients, as already mentioned. And Belinda too. The current clinical studies are based on chemotherapy. And it was always like that, the more you give patients, the more cancer cells die. But studies also show that when it comes to chemotherapy, more is not always better. But especially in immunotherapy and There is a hurdle to targeted therapy. And once you achieve that, that's it Drug effective. And beyond that, the toxicity becomes higher. So you shouldn't give more than necessary. But that's complicated. There is also pharmacodynamics and kinetics, which are used to measure how effective the drug is for the patient. So it's more complicated than just the quantity. My goal is to find out the minimum effective dose. We are still a long way from that. But we are making progress. And that is always positive. I think it would be a good idea to do the clinical trials, to start their design again. Because they were designed for a different era. And now I want to we include more points so that this new generation of medicines can be better evaluated. There are also chemotherapy and immunotherapy for targeted therapies, so that these drugs can be used more efficiently. This is all from me. And we have 15 more minutes for questions. Thank you for your talk, Lee. We're going to the now To ask about. And the question was whether we would eventually discontinue the links, the Lee people. Yes, I wanted to type that in, but then I was lured out. Sarah is doing this right now. Naturally we will do that. We are posting the links. Janis, would you like to tell us about your experience? regarding this topic? Janis, are you still with us? Yes, sorry. Could you ask the question ask again? Would you like to share something about your participation so that the audience knows how do you get involved? Regarding mine, I have been a patient advocate since my diagnosis seven years ago and I've known one for a long time. I was very interested in the research that the PCDI was conducting and also offered to share the surveys with them the patients of the group with the tasing of the breast cancer groups. That was my role at the beginning. So I helped distribute the surveys and get patients engaged and in In 2021 I joined the PCDI as a member. Thank you. We have different ones Questions and also from members of the TAS program. We can't answer them all. We will but do our best. Berlin, what are some of the misconceptions that people have about the outcomes reported by patients and data? Lindy, I can start. I think in terms of the first studies, you can't compare a lot of things, but other clinical data are often not comparable. We also have additional data the subjective side, but clinical data is also sometimes subjective. There are also points here, that are not perfect and that's why I think that sometimes we have to look at the results of the patients, the patients report are not that important. But I think that's not true. If we Collect data in just one treatment group, then collect data treating everyone the same become. And that's one of the topics when we talk about the first clinical trials. But Maybe others have more I can say about this. When patients have an idea of what to expect in terms of side effects, they are easier to deal with bear. For example, I didn't know about peripheral neuropathy and so I didn't know that my hand might feel burning if I touched anything. It would have been good, knowing this so I don't have to call the oncologist to say my hands burn. If you know what to expect in terms of side effects such as vomiting or diarrhea, you can reduce these side effects. But only the knowledge of these Possibility helps. One of the factors that is confusing is the side effects the weight. After three months you may have already changed the treatment and then you will know not whether it was the first treatment that caused this side effect or the second. Often Patients don't know that side effects can only occur later. With immunotherapy You can have side effects for years afterwards and your family doctors are not always aware of this consciously. They then don't know if this is a side effect of medication so he takes them sends you back to the oncologist and then they try to use other types of treatments. One further question. When participating in a Phase 1 clinical trial, are multiple doses evaluated and doesn't that delay approval of the drug? I think we don't have enough information and the FDA is promoting trials in which different doses are approved and they now want to study in phase 2 that patients have different doses doses are assigned. We need to have additional safety data for this and I believe there is room for that. I don't know if this will delay things. That will happen discussed, but in phase 3 you often have the wrong dose or a non-optimal dose. I would say if there is a small delay due to the wrong dose in phase 3, and then when we look at Belinda's timeline. She showed that phase 1 is so short for this multi-year timeline. Even if you double or triple it, it doesn't matter major influence on the time until approval. You talked about that the dosing strategy should be implemented in the phase 1 study. Are dosing strategies different in phase 2 of the Studies? I think there are variations. These continue to evolve as we speak, but to have the foundation we need to understand what is mostly done. In the Phase 2 this is fixed. There are opportunities for doctors to make changes to doses in the studies in phase 2 and 3. This will be specified in the study protocol. There are guides how you can reduce the dose. In phase 3 this is based on what is generally in the clinical practice is done. Normally changes to the protocol are then made. Is that the correct answer to this question, Janet? That's okay, thank you. Once the dosage strategy has been determined and the drug is approved, how is the dose information communicated to the oncologists and can the oncologists change it compared to the what was done in the studies? We discussed that. It's a little complicated, but basically the FDA says they don't regulate the practice of medicine. If we then go into clinical practice, then sometimes there is a phase 4, which is observation after the introduction to the market and this can also be included in cans. At this stage you can they change the assessment of treatments to give people longer breaks. There is a series of things that can be discussed with FDR, together with the sponsor, to make changes to be carried out. But there is always information on the label, but there is also in the study protocol Information about this. It then becomes a little more complicated and we have cooperation groups that provide additional... Conduct studies to better understand these problems. People talked about the HIV pharmaceuticals that were exported by the IH. There was a drug where they dose according to the approval changed. That was capsidabin, a chemotherapy drug, and the oncologists in PCDI have shared with our group that many oncologists are not taking the full dose prescribed that they saw such great toxicity. You've gone under the dose, which were specified on the label. This made a change to the etiquette. We only have a few minutes left. I want to give you each a minute to conclude be able to share thoughts. Janice, do you want to say something? Thank you. I think that workshops like this are incredibly important. Because we not only educate other patients and patient advocates, but also clinicians. And we emphasize the importance of the individual adapted medicine and the optimal dosage for patients. Because with the dosing breast cancer the treatment is not a sprint. And as we have already mentioned, these cumulative side effects or subsequent side effects can have a negative impact on quality of life of patients have. So if we do things right sooner, then patients need it Treatment may last longer and in return they will have a better quality of life and a longer life. This is of course true for lung cancer patients and others too. I think, what we must take into account is that each of us is a unique individual. We are different in terms of race and other including our unique goals. And with everything too With these great initiatives from the FDA and others, we believe it is very meaningful for doctors and patients is to take into account physical characteristics of patients, like body mass and also their goals in life. And together we should find the best dose for you Patients are determined. Another reason for this, and everyone knows this, is in the clinical ones Studies subject patients to very strict inclusion or exclusion criteria, but that's not the case in the real world. This is completely different and that is yet another reason that it is important to include patients' opinions. I just want to say that we are remembering that we are the experts in our own illness. And if we combine that can with clinical knowledge, then we can be much more efficient in helping researchers Bringing drugs to market that improve our outcomes, as well as everyone else's, who have the same diseases. Thank you. Belinda. I can't say much about that. The Rest of the people said a lot of interesting things. As a researcher myself, working with Lee and Janice. I have worked with Ann and Lee for years, as well as Janet. And it was a pleasure to work with them and combine the researchers' knowledge with theirs. And my door is always open to exchange ideas, because I think their opinion is very valuable. I would like to thank all participants for this Explanation of how dosing works, but also the patient perspective and how patient advocates can participate, participate in these types of groups. Thanks for your participation in this webinar and see you again.

patient data

clinical trials

patient-centered dosing

treatment outcomes

patient report outcomes

Patient-Centered Dosing Initiative

misconceptions

phase 1 clinical trials

collaboration

individual patient characteristics