Brigid: Good evening and good morning, everyone. Welcome! I am your host for today's Coffee and Conversation - my name is Brigid. Coffee and Conversations is a monthly interactive sit down event hosted by CSOFT. Every month we'll feature honorary guests and experts from a diverse range of industries and fields to lightly discuss topical themes important to the life sciences and language services industry. So sit down and relax, pour yourself a coffee or a tea or hot drink and enjoy!

Brigid: This month we are joined by our special guests Dr. Vladimir Misik, Partner and Founder of longTaal, a clinical trial informatics company, Partner and Co-founder of VIARES Academy, a Vienna academy for clinical research, as well as a board member at SanaClis, a full service European CRO, to discuss geographical clinical trial market trends - evaluating market share and industry investment, and the importance of clinical trial reputation index for global drug development. 

Brigid: In our previous Coffee and Conversations episodes, we have discussed the global clinical trial industry through the lens of patient diversity and through patient recruitment. In our Coffee and Conversations with Professor Victoria Elegant in particular in episode three if you haven't done so already, we recommend that you give that a listen. But in that conversation, we lightly discussed and touched upon how the cost of clinical trials no longer drive investment and pharmaceutical sponsorship into a particular region. In this episode, we will further elaborate on this and discuss a new lens for better understanding the global clinical trial landscape and future trends in the market. 

Brigid: Okay, now let's introduce today's guests, Dr. Misik and Ms Shunee Yee. Dr. Misik is the Partner and Founder of LongTaal, Partner and Co-founder of VIARES Academy, as well as a board member at SanaClis. With 30 years of biomedical R&D experience, Dr. Misik has held a range of previous roles within the industry and in academia, working as a VP and Head of Global Centralized Operations Center, Global Clinical Operations Leadership Team Member and Regional Head of CEE and MENA at Quintiles/IQVIA. Dr. Misik has published extensively on various aspects of globalization of industry clinical trials, contributed to oncology research at the National Cancer Institute in Bethesda in Maryland, as well as Cardiovascular Research at the George Washington University, School of Medicine. Dr. Misik is an Editorial Board Member at Applied Clinical Research, Clinical Trials and Regulatory Affairs as well as a member of the DIA Global Core Committee for Clinical Research. Welcome, Dr. Misik. Thank you for joining us today!

Dr. Misik: Thank you very much!

Brigid: Ms. Shunee Yee is the President and the CEO of CSOFT International and CSOFT  Health Sciences, which provides end-to-end medical translation services for all phases of the product lifecycle, market access consulting, medical writing, and CTD/eCTD  submissions with the FDA, EMA and NMPA. Shunee is passionate about education and has contributed to the Michelle Obama's Let Girls Learn Initiative, the Hopkins Nanjing Center for the Chinese American Studies, and the Dexter Southfield School. Additionally, Ms. Yee served as the Co-chair for the Joslin Diabetes Center's A Taste of Ginger 2021 Committee supporting the Asian American Diabetes Initiative, or the AADI. Welcome Ms. Shunee Yee and Dr. Vladimir Misik - the floor is yours!

Shunee: Thank you so much, Brigid! Good afternoon, Vlado. We are so excited to have you join us today. I have my coffee ready - I'm sure you do to!

Dr. Misik: Yes, I do – I’ve got my proof here!

Shunee: You and I discussed that, you know, hopefully, we talked about wine, hopefully soon we can travel we can raise the glass together - that will be wonderful! Before I start my questions today, I would like to pull out a couple of graphs you used during your keynote speech at Clinical Trial Euro graphs would give our audience a little bit of background of past and current global clinical trial trends landscape. 

Shunee: So before 1997, North America, and Western Europe countries own pretty much the entire global clinical trial market. So there is a major geographic shift of global clinical trials sites that took place between 1997 and 2010. During this time, the developed countries lost a significant share of close to 30% of the market share to emerging markets, or to the rest of the world. This outflow trend from developed countries to emerging countries continued to 2012, but appeared to slow down from 2013 to 2019, with developed coutries somehow managed to retain more than 70% of the market share. So my question to you Vlado, is what triggered the geographic shift between 1997 to 2010? Is cost the driving factor? What are the main reasons behind the developed the countries and how they managed, were able to stop and partially reverse the outflow to emerging countries? 

Dr. Misik: Thank you Shunee, for that question. I just I just laughed when you mentioned my keynote in Barcelona in 2019. That was the year when we still traveled to conferences! These days, we, we take video conferences. So anyway, something happened, as you have seen from the graph, something happened in 1997. And I would say 1997 is really the year where the word global competition for clinical trials started. What happened in 1997? It was the year of adoption of ICH-GCP as the International Guidelines for Conduct of Human Clinical Trials, which defined criteria based on which data from any country which adheres to the criteria would be acceptable by the US and European regulatory authorities. 

Dr. Misik: And you have seen that immediately kind of a precipitous decline of market share of the developed markets, which pretty much owned clinical global clinical trials until that point started. And what I like to do always imagine when we looked at the two trajectories between 97 and 2002, it looks like somewhere around 2000 to 2010, the graphs would kind of cross over, then the majority of clinical trials would have been conducted in the emerging markets. We of course, know that has never happened. 

Dr. Misik: So the question is why that never happened? Well, it never happened because of a number of things. First of all, the large markets, the developed markets, they realized the risk of competition, and they adopted measures to counter that - they've a very strong economic muscle, they are the largest consumers of pharmaceuticals, and they utilize that muscle to reverse that. Secondly, the clinical trials have gotten smaller, no longer 10s of 1000s of patients are needed such as in the in the early 2000s. Now very surgical small clinical trials, which utilize biomarkers can be conducted. An example is the approval of Xalkori, which is used in in treatment of rare several lymphomas where the whole study was based on the product was approved based on a study with 124 patients only! So that is why that there are additional factors, of course, but the combination of the of the strength and the muscles of the large markets, combined with the trials getting smaller have been the main contributing factors why the outflow has stopped. 

Shunee: Yeah, so Vlado, maybe just kind of for our audience, can you, so in terms of the investment by countries to the new product development, is that you know, could you kind of elaborate on that a little bit? You know, that's another set of data. Do you see that there are consistent developed countries that are continuing to put a lot of investment into new drug development? 

Dr. Misik: So I was referring to the investment which is made by pharmaceutical companies who conduct clinical trials in the various countries. Of course, if a country adopts measures which are attractive to sponsors of clinical trials that would that would attract and bring the clinical trials sponsors to that country, and indeed, the large clinical trial markets have done so successfully. 

Shunee: Right, right. So, you and I discussed about how the global clinical trial market competitiveness of a country is defined by this two main factors, right, the importance a country’s own pharmaceutical market as the driving factor, and which is proven, the market itself is important. And the other thing is the clinical trial competencies. So, could you elaborate on that? You mentioned about how biopharmaceutical sponsors of a clinical trials, when they make decisions, they evaluate a combination of those two set parameters. So, could you elaborate on those principles? And what can a country do to increase their competitiveness? 

Vlado: So one thing that countries can hardly do to really make itself such an important pharma market that they start consuming large amounts of pharmaceuticals, that, let's put that option aside. But so but what countries can really do is to increase and improve their clinical trial competencies, let me be specific. It is the decision to place clinical trial is based on the perception of difficulty to conduct a clinical trial in the country. It is regulatory complexity, it is the duration of the clinical trials startup, it is the ease of site contracting, those are the those are the usual complexities, import/export procedures, and of course, proven ability to deliver in a given indication based on historical data. What is also important is government actions. Governments have a big role to play. So what can governments do? They can adopt financial measures, which make it attractive to conduct clinical trials, including R&D tax breaks, France is very good at doing it, Canada, Austria, but also its operational, non-financial measures, which governments can do. And it's, it's particularly the ones creating one stop shop for sponsors of clinical trials in the country. Let me give a few examples: the UK, by creation of the National Institute of Health Research has created such a one stop shop. Siimilarly, Korea with their Connect initiative, which is also utilizing nationwide electronic hospital records for planning of clinical trials. Denmark, with our Trial Nation, as well as Malaysia with Clinical Trial, Malaysia. So those are examples of government level initiatives. 

Shunee: Fantastic! So, speaking of that, I know recently you introduced the country Clinical Trial Repetition Index, as the additional dimension for evaluating relative attractiveness of countries’ clinical trial markets. So this is also from one of your keynote speeches. And I’d like you, to explain the differences between participation in clinical trials versus participation in consumption of pharmaceuticals. So why higher consumption of pharmaceuticals doesn't really guarantee higher clinical trial market share? So can you give a couple examples, how country Clinical Trial Repetition Index can be utilized by various different stakeholders? 

Dr. Misik: So first of all, how did we get to trying to quantify something which is as seemingly soft and subjective as reputation of country? We were certain in our assumption that sponsors of clinical trials do not act irrationally. Indeed, it is in the best interest of every pharmaceutical company to maximize return on their collective investment of $130 billion, which they spent annually in 2019, in conducting clinical trials, out of which $50 billion for recruitment of clinical trial patients. So, we started with looking at the picture of global clinical trial allocation and assumed that surely, there must be a logic in how that happens. So, what the graph which you have shown actually attempts to do is to look at, what is the potential return on investment in terms of future prescriptions in the country that call it pharmaceutical sales market share? And on the on the Y Axis, there was there was allocation of clinical trials. And you would, of course expect since pharma behaves rationally, that it would be a perfect alignment around market share of clinical trials roughly equals the market share of pharmaceutical consumption, which actually is true for majority of the countries. But there are a few outliers. And indeed, those are the countries which offer something unique, which is not necessarily the pharmaceutical sales market, but they offer different value to sponsors of clinical trials. And I made a reference in my previous input regarding clinical trial competency. So those countries, which are outliers, and they enjoy high allocation of clinical trials relative to their footprint, they offer exceptional value. On the flip side, are countries which do not, they, consume pharmaceuticals, but they do not participate in development of those two significant events. So that is roughly what happened. 

Shunee: Yeah, well speaking about outliers. And can you give two extreme cases, like examples? So, using one example, like which country is an outlier in terms of not necessarily, represent the bigger percentage of a consumption of pharmaceuticals, but somehow, they have additional value to offer. So those still kind of enjoying a high percentage of clinical trial market share. 

Dr. Misik: So, the outliers are actually very few and easy to name pretty much all. As, as a regional bloc, Central and Eastern Europe has defied gravity, and indeed, has enjoyed over proportional allocation of clinical trials. Israel, and among the European, Western European countries, Belgium, so those already outliers on the high research attractiveness. There, there are outliers on the low research attractiveness. And as a region, it is the Middle Eastern countries, particularly except of Israel, which is on the other side. So, the Arabic Middle Eastern countries are hugely underrepresented in allocation of clinical trials. 

Shunee: Right. Right. So, but isn't that gap between, you know, represented that I guess, in your formula of the Reputation Index, is there kind of an opportunity for individual countries for improvement? I think, you know, one case you and I discussed about how Japan, how they have evolved, between 2012 to right now, and have become a major clinical trial market representation in entire Asia. Can you elaborate on that a little bit more of what happened in Japan?

Dr. Misik: Sure. The so the reputation index, or the position of the country on the axis between allocation to research, relative to consumption of pharmaceuticals, is actually a fairly good predictor of the movement of the clinical trial market. You mentioned Japan, indeed, almost 10 years back, Japan, we have seen that Japan is in this unusual position, which in our view was not sustainable, which was significantly underrepresented in development of new pharmaceuticals. We predicted Japan's clinical trial market would grow, which is in indeed what happened. China has been also in relative terms underrepresented in clinical trials and China has been the fastest growing clinical trial market globally, driven particularly by still the existing gap between consumption and development. 

Shunee: Wonderful! So, I guess this is a bring me to my last question, Vlado. So, we talked about how this innovative biopharma sponsored clinical trials create a significant the economic value from tracking investment to creating jobs to you know, allowing patients to benefit from cutting edge therapies. So, we know this global clinical trial market will remain to be competitive. So Vlado, can you give us your prediction of the next five years for the global industry clinical trial market trends and what advice would you give our audience today?

Dr. Misik: Thank you, Shunee. Since I don't have any crystal ball handy, I will look into my coffee cup and give you my bold predictions. What's going to happen? Of course, as a scientist, I always I don't like to give predictions because there is a high probability of error, but you know, let me try my best based on all information that we see. We predict that developed markets will retain, successfully to retain, their existing market share, and some of them will even grow it. The only emerging markets which will enjoy continuing growth will be China. Central and Eastern Europe as, as the most successful region of the previous decade, will lose, is likely to lose market share in clinical trials. And as far as the trends which will happen, it is technology that will define clinical trials of the next decade: It is the decentralized clinical trials, remote clinical trial competencies, usage of wearables. So, you know, the CROs, which will be successful and the sites, clinical trials sites, which will be successful, will be excellent users of technology and early adopters. With all the technology that will be required, one problem of the industry is likely to remain in the next few years, is the shortage of clinical trial resources, particularly the clinical research associates, which are, have been in short supply for a number of years, and there's no sign of that of that trend changing. So those are my predictions for the next five to 10 years.

Shunee: Thank you so much, Vlado. So, I can't wait maybe a few years later, you and I sit together again for another Coffee and Conversation and look back at the data as to and you know, compare with your prediction. Thank you so much! Let me give it back to a Brigid. So, to see any of the questions from our audience. 

Brigid: Hi thank you, and what a fascinating discussion! We have a couple of questions from the audience, Vlado, and I will bring them up for you. One is about how Clinical Trial Reputation can better inform health policy. So, the question is, you spoke about financial tax incentive measures, how can the clinical trial reputation index better inform health policy on a global level, and can you give examples from country to country? 

Dr. Misik: Sure. So first of all, you know, now that we have calculated reputation index, what do we do with it and or how can it be practically utilized? So first of all, we've seen the use cases are roughly for, for the reputation index, we have seen some reluctant sponsors, we have our new, smaller biotechs who are new to moving outside of the US, to be guided by behavior of larger sponsors to go to countries unknown to them. So, Reputation Index kind of provided helpful guidance for the new entrance to global clinical trials outside of the US. The second use case, and I believe that's more in the heart of the question, is what can governments do, how they how can governments utilize that data to demand a fair share of clinical trials? Let me give an example of one country with a government of which I've worked closely and that is Saudi Arabia. Saudi Arabia is a rapidly growing pharmaceutical consumption market, they are hardly scratching it however, the surface of the global clinical trials. So basically, the government realized looking at the reputation data that they are consuming pharmaceuticals in development of which they have not participated in and they are now having discussions with the with the pharmaceutical manufacturers about balancing the two. So that's an example what governments can do with that information. Similarly, patient organizations broken down into therapeutic area, they can see by country, which countries are underrepresented in a particular therapeutic indication and patient organizations can demand a fairer share of the Global Development. We’ve seen another use case is the media utilizing the data to counter the concerns by population that they are being used, the population is in the country is being used as guinea pigs in development of new pharmaceutical products using the data. The journalists in Egypt were able to demonstrate that actually the opposite is true. They are not guinea pigs in clinical trials. They are consuming pharmaceuticals in development of the which they have not participated. So that's another use case. And, importantly, it can also be utilized to make predictions about market trends. I gave an example of Japan, which based on the lower position, we predicted it must grow. And so those are the four use cases for the for the reputation index. 

Brigid: Right, thank you. And I guess on the flip side, another question that has come in what country what can countries do to incentivize more sponsors to conduct more clinical trials and their markets? You spoke a little bit about this in the conversation with Shunee, but how can countries be more competitive? 

Dr. Misik: So, I would say there, there is a government level, let's first look at what countries at a government level or national level can do. So, putting the financial incentives aside, operational incentives, in majority of the countries the government has access to, to electronic hospital records, there is only a handful of countries which are utilizing the power of electronic hospital records. And it is indeed one of the strongest weapons. It is about improving the precision of clinical trials. That is a large area, which very few countries have tapped into. Outside of this, is looking at the bottlenecks. If, let's say import/export procedures, or lengthy clinical trials startup processes or lengthy regulatory approvals are a bottleneck, those need to be addressed at a governmental level. At an institutional level of the level of hospitals and clinic research centers, it is about professionalization of clinical trial sites. The treating physicians can no longer be competent clinical trialists is without a professional clinical trial support. So availability of professional clinical trials support study coordinators, is a key factor. 

Brigid: Great, thank you. Unfortunately, those are all the questions that we have time for today. On behalf of CSOFT Health Sciences, we sincerely thank you Dr. Vladimir Misik, or Vlado and Shunee for a fascinating discussion and insightful discussion on the shifting geographical clinical trial trends and market investment. If you would like to further look at LongTaal’s clinical trial analytics, you can check out their website at www.longtaal.com. If you love this podcast episode, we highly recommend for you to catch up on our previous episodes. You can find us on any major podcast platform as well. You can search us on CSOFT’s Coffee and Conversations. To everyone attending online or wherever you are in the world, we hope you enjoyed this installment of Coffee and Conversations. Bye for now. Thank you, everyone. 

Shunee: Thank you! Thank you everyone, thank you Vlado!

Dr. Misik: Thank you for having me!

Thank you for listening to this month's coffee and conversations. For more information on CSOFT’s services, visit www.csoftintl.com for more information.