So my name is Gunver Kienle. I'm coming from Freiburg, and we have an own institute there, the Institute of Applied Epistemology Medical Methodology, which is affiliated to the University of Witten/Herdecke, and I also work at the University Hospital of Freiburg, and I just don't research, my main focus is on research in the area of anthroposophic medicine and particularly, mistletoe but also on other topics. In my other area of expertise with a lot of international interest now is on high-quality case reports. So, yeah, this is my affiliation. So, I would like to ask you regarding challenges in research of anthroposophic medicine especially in the realm of of oncologic care or supportive cancer care, and to ask you what are the challenges in designing studies and making research in these areas? So, one basic thing is that anthroposophic medicine is a system approach. It is highly individualized to the patients, and it uses standard care, standard conventional treatments, but also anthroposophic treatments depending on the situation of the patient. So, in real anthroposophic contexts, you have complex multimodal intervention, which has to be thought about if you do research. But they use certain interventions that are also used very widely outside of anthroposophic medicine, like for instance mistletoe, mistletoe therapy. This is used very widely by cancer patients about by 50 percent roughly, Germany or Austria and also outside. In this situation, you can do conventional research more easily than in a system approach. So altogether, for anthroposophic medicine, I think we need a strategy for research. So, we need conventional large randomized controlled trials for a certain collection of treatments, like mistletoe. But for the all the other treatments, you also need other methods because you can't investigate all interventions in all situations of large trials, this is not doable. So, you need other methods like smaller trials, like the cohort studies where you do analysis on certain interventions on good case reports. So, I want to start with mistletoe and large trials. Mistletoe is an intervention where you can really do pick trials, and there are a lot of trials being done. One of the best is by Dr. Troger conducted in Serbia, launch trial with 220 patients with advanced pancreatic cancer. It's a modern trial with the modern methodology, how you are supposed to do it. Randomized controlled trial, where mistletoe was applied additionally to usual care, and they had a significantly longer survival under mistletoe. But what is really remarkable is that the patient did much better. They had much better quality of life. While usually patients with pancreatic cancer lose weight, they gained weight, and they had less pain, so they did much better. So, this is a very good trial. Had a very positive result, and we are currently repeating this trial similarly, but even more advanced, awesome now with a placebo control group in a country of high medical care, high medical standard in Sweden. Serbia, you could say as a critique, Serbia doesn't have so good cancer care, than we have Germany or Sweden or Israel or the United States. But Sweden is really a country of highest cancer care. So, we repeat this trial or we also conducted a trial there, randomized-controlled trial, placebo-controlled with 290 patients with advanced cancer, that either receive chemotherapy or not, and they additionally get mistletoe therapy. The primary question is does mistletoe have influence on survival? The secondary questions are, does mistletoe have an impact on quality of life and on weight? We also embed a qualitative study in there, to see what patients say, and it's ongoing and it's going well. So basically, you study the Viscum album or mistletoe, which is old herbal operation which is very unique in anthroposophic medicine, but you studied in conventional methodology and in randomized controlled trial, placebo control. Yes. If I understand correctly. Yeah. You raise a very important issue. I just want to complete that three other very interesting trials going on or currently prepared. One is a large randomized control trial on this mistletoe therapy in bladder cancer, mistletoe installation after surgery. They want to recruit about 600 patients in Germany, and the other trial just started a Phase 1 trial. Also conventional trial, Phase 1, 2 trial at John Hopkins University, intravenous mistletoe therapy, and the third trial. For which indications? Several indications. It is Phase 1, Phase 2 trial. It's intravenous mistletoe, why you usually give it subcutaneously, and the third trial we prepared is the trial on mistletoe therapy in glioblastoma, newly diagnosed glioblastoma after the surgery, parallel to chemotherapy and radiotherapy. This is what we conducted in Mass General in Freiburg and some other hospitals. So, but as you said correctly, this is just one methodology and these randomized controlled trials are very important to basically prove the efficacy or test the efficacy. But there are many, many questions, important questions that cannot be answered by randomized-controlled trials. So, you also need other methodologies. The other big questions are the improve the application of mistletoe, optimize its application in several indications. To conduct such a trial like in Sweden, like glioblastoma trial, it takes a long, long time to prepare these trials. It is really not very easy. You have many competing trials. So, it's really not very easy and trials are very expensive today, confirmative trials. So, you can just do a very few and you need other methodologies for all the other cancer types and cancer care questions, and certain situation which you just have a few patients, so you need other methodologies for these. This is very important. In these different methodologies, they compliment each other, and they give you a more comprehensive answer to all these questions that you have as a clinician. So, how would you explore a whole system, a whole system approach, like anthroposophic medicine or for example, in our area in the Middle East, there's a lot of traditional medicine and sometimes, if you minimize it to specific herbs, you lose the context. I assume that some people just claim that if you take for example, the mistletoe out of anthroposophical holistic approach is a kind of minimizing the meaningfulness of this remedy, which is not just its connection to the body but to other areas like psychological effect or spiritual effect and so on. So, how do you study, how do you explore the whole system approach, where herbs are one part or one ingredient, let's say from a much more sophisticated biopsychosocial-spiritual approach? This is very important. The randomized control trial on one herb is like a look through a keyhole, very precise but very narrow, and whole system approach can be investigated and should be investigated with different methods, like cohort studies. We have done a large study on anthroposophic medicine, not specifically on cancer but on chronic diseases, where you can capture all the indications, and you can look for certain outcomes. So, you can do this. This is a very good way and you have to think about how to deal with the control groups. There are different possibilities how to do it, and other very interesting aspects are also case reports, high-quality case reports, where you can really go into the details and really outline how you view the patient, what you see, how you decide on certain treatments, what you do on your approach and your thoughts, and what the patient's responses are. The patient can also participate in these case report. So, case report is really a very unique tool to capture complexity and all the processes exemplary. Case reports with high quality where you can really give insight in what you're doing and how it is working in the patient. So, this is a very important complementation and of course cohorts to this. It's quite common in integrative oncology practice that you see patient and you evaluate patient's concerns and well-being and quality of life issues and you just design a preliminary treatment program that resonates with patient's beliefs, with the evidence concerning the effectiveness, safety, communication with the oncologists, and so on. But as time goes by, from one week to another, there is a change and modification in the treatment goals in the hopes that you'll use for other modalities. So, if you look it through a process of six weeks or 12 weeks treatment, weekly treatments, you see that it's not like in randomized controlled trials were you just start and you want to conclude with the same remedy. If you don't, you talk about dropout and things like that. But this is the natural cause. So, how would you evaluate these complex patient tailored approach? Well, it depends whether you want to look on the process or whether you primarily want to look at the outcome. If you want to look at the process, I think the primary methods are case reports or qualitative research where you can describe it. Whenever you do larger studies, you can't go into many details anymore. You can do outcome studies like everybody can treat how they want, in what way they want and you look at the outcome. Do they become better? Another issue is you sort of have to sort all the questions in there like the safe articulations, which are very important. They again need approach on a more population level. So, you could in an extra project, you can assess the safety of your drugs. But to show the processes and to show your outcomes, you either have to go on the individual level or you just investigate the whole context, the whole cohort like more in an effectiveness study, everybody can do what they want to do and look for the outcome. But then in the cohort studies, you can't look into the individual process, not very much. So you could also do a big cohort study and implement some case reports in there. Where you really give insight into the processes. But really look into the processes you need case reports or qualitative methods. Okay. I would like to ask you about another question regarding research, and that's the cultural challenge that you face now in Europe regarding immigration from the Middle East and North Africa and I understand that you are challenged now with the growing community of patients that came from these areas, which mainly have affinity with traditional medicine in the Middle East. Herbal medicine in the Middle East, they have other health challenges of course that they are facing now, acute. Maybe there would be other challenges which would be sub-acute or chronic diseases that would be challenging them in the years to come. How would you relate to research in this community, do you think if there's any role to integrative medicine in bridging the gap between conventional European medicine and that sort of traditional medicine orientation that is more prevalent in the places they came from? So, what's the role of integrative medicine in between and how would you research that? The role of integrative medicine with regard to refugees, there are two, two roles at least. The traditional medicine that the refugees come from and which they know and they may want to use and the integrative medicine we have here, which may be well suited to treat certain conditions of the patients. So, there are two aspects. To give an overall introduction, the refugees really are omnipresent in our life now. They're everywhere, they're in the midst of our lives. So, the total cultural background to have an understanding and to get close to their cultural background and they to our cultural background is very important also for their health. Because they come here often traumatized and they are in danger to get an additional traumatization here because of cultural gaps. So, the first thing is that we better understand their cultural background and they understand our background in order to prevent an additional trauma. Well no, this is too much. We have no understanding at all on the role of their cultural background, their traditional medicine and the importance of their traditional medicine or integrative medicine for their health care needs. Currently, we have no knowledge about this. We just know from some other countries that this is may be very important. So, first step would be to inquire with qualitative methods first and then with questionnaires about their background and how important traditional medicines are to them. So, this will be first thing and to make this known among practitioners in Germany, but be very important. Then another very important issue is our complementary treatments, our integrative medicine has a lot of tools, which may be well-suited for the health conditions of refugees like trauma, like mental healthcare conditions, psychosomatic conditions, acute infection, but are these methods that we have, can they be offered to refugees? Because of the culture difference. For instance, if you do music therapy for mental condition, it works very well here, but is it something to accept for Muslim people or do they think, no music is nothing very good and if I go to the doctor, I have to get a drug. So, there are some culture difference here to our approach or we have very good success particularly in mental conditions with bodily treatments like imprecations like massage, like packages, very helpful here. Also in palliative care, but maybe the people have a hard time to accept them because they have a different feeling for their body or may not accept bodily intervention. But there are a lot of very, very good intervention from integrative medicine that could be applied for refugees and could be investigated whether they work, it helped them. But you have to do pre-studies whether they are actually appropriate for them.
