SGS SA (SGSN) Earnings Call Transcript & Summary

Welcome to our today's webinar, Setting Up COVID-19 Clinical Trials During the Pandemic. Please remember, you can ask questions throughout the whole webinar by using the widget at the bottom of your screen. All questions will be answered at the end of the webinar. Our presenter today is Dominiek Staelens, who's International Project Manager at SGS. Dominiek holds a PhD in Biomedical Sciences and has more than 5 years of experiences in clinical research. Dominiek, the floor is yours.

Thank you, [ Jana ], for this introduction. So let me please go over the agenda for today's presentation. So first of all, I will discuss the feasibility of COVID-19 trials. Later on, I will move forward to regulatory review and protocol development. Next, site selection and activation, and study setup as last topic for this presentation. And finally, I will wrap up the presentation. So to first set a bit the setting of the scene -- of this presentation. So COVID-19, it's clearly a booming trial industry. So for now, there are more than 3,500 COVID-19 trials, which is quite impressive, if you remember that, that disease was only identified end of last year. So of these 3,500 trials, the very vast majority of studies, so more than 3,400 studies are therapeutic and around 120 are vaccine trials. And there are a bit less than 2,000 interventional studies. If we go a bit more in detail or in-depth regarding the different phases of the study, then from Phase I till Phase III trials, there are more than 1,000 trials that have started since January of this year. And currently, there are now a bit less than 1,000 trials that are recruiting, and they need more than 380,000 patients. So on the graph on the right, you see the different studies that have been initiated this year. And you see in the orange graph, the accumulative number of patients that need to be recruited or have been recruited so far. So as of this month, October 2020, more than 450,000 patients have been or are aimed to be recruited. This is clearly demonstrating that current setting of COVID-19 studies, it's a booming and a competitive field. Before I move forward to the next slide for the first topic regarding feasibility, I would like your opinion regarding COVID-19 studies and then to get a better understanding of your experience. So what has -- what do you feel has been most challenging: the unclear health authority guidelines, health authorities' expectations regarding COVID-19 trials, the competitive landscape, a high workload for investigators and staff or other? I'll give you some time to reply to this poll your answers. So I will move forward to the next -- or the first topic inside of this webinar, so which is feasibility process. So our standard process is to choose regions and countries based on disease prevalence, right? We know normally that the disease setting, we have a short list of sites based on experience in similar trials. And it's mainly the PI who decides whether he or she is interested to participate and if it's feasible to conduct that study at his or her institution. And we received recruitment estimates, which are based on performance in previous studies. So the feasibility process, you can get a clear picture whether sites are capable to run a study and what are their recruitment projections. The challenge with COVID-19 studies is that there is no reference framework, right? It's a disease that was only identified end of last year. So we also -- there's an unknown evolution of epidemiology and for the country selection, it has a clear impact because it wasn't really known where the biggest incidents in countries will be or even within one country. There is clearly an overwhelming number of competing trials, as I explained earlier on. And there are different feasibility decision processes at many sites. So that's clearly a challenge to streamline the whole feasibility process. Some centers can't cope with patients and studies, which could bring us to more smaller sites, for example. But there, then you have, of course, the issue or this challenge, at least, that they have less resources and less experience. And as for any clinical trial, definitely for COVID-19 studies, the timing is important. Sponsors are eager to start within weeks. As a mitigation at SGS, what we have been put in place is we ensure a close follow-up of the epidemiology data, regional and at a worldwide level. So the Johns Hopkins data was clearly of added value there. We also increased intensity to contact sites. So we really very closely followed up with sites, and we even recontacted sites when there was a new wave in the region. Also the feasibility question, it was short and bare minimum to make -- well, to facilitate the review process and to make sure that sites are not discouraged by a very lengthy feasibility questionnaire. Also the start-up process, we tried to fasten it with site activation in parallel of still going ahead in the feasibility process. And a well-written and attractive protocol is clearly of added value so that investigators rapidly understand the study that you want to conduct at their institution. Based on our experience, the involvement of a sponsor to connect with critical sites is of high added value. In the next, regulatory review. So per standard process, normally, we have fixed time line for review by the authorities and also the ethics committees. And some countries, for example, in Belgium, there are normally waiting periods to submit protocol amendments. And in different setting -- and in other settings, we know the regulatory expectations rather well. And we, for example, know what is important for ethics committees or authorities in terms of end points or eligibility or safety assessments. The challenge here again is that it's all new. So it can be difficult to understand the changes in the processes of time lines. Then also, there is no real framework for health authorities regarding study requirements. And their review process is also changing in function of the COVID-19 pandemic. For example, in France, initially in spring of this year, there were shortened time lines for the review process, but then with the decrease in patients and also the very high number of studies, this expedited review process was stopped. Also another challenge for the regulatory review is that the quick approval process, which is obviously an advantage, has also the challenge that you need to reply very fast. And if you have -- if you want to conduct the study in multiple countries, these time lines not always coincide. So it can be difficult to manage the multiple protocol amendments or changes that have been requested by the authorities. So as a mitigation plan, so in general, as mitigation plan for a fast start-up, as I said before, some authorities shortened their review time lines. I already mentioned Belgium, which, for example, also in U.K., the MHRA gave very, very fast feedback. So we were able to have regulatory approval sometimes within days. As an EMA guideline, they clearly preferred VHP, so the voluntary harmonized procedure, where you combine a regulatory submission in the countries of -- the European countries. So -- and one, so that would mean that you also get a combined feedback from the authorities. Another mitigation is to consolidate feedback from different health authorities where possible, of course. So the idea is there that you run the submissions in parallel and that you try to combine different feedback that you get from authorities in one bigger protocol amendment. And you can also work with placeholders for team meetings upfront so that you can discuss already -- that you can already anticipate on expected feedback that you will get from the authorities. Moving to the second poll of this presentation. So have you seen indeed shorter health authorities time lines for your COVID-19 trials? Is this the case for you for nearly all of the countries involved? Or more or less than half of the countries involved? Not that much? Or it's not applicable? I will give you some time to answer to this poll. Next topic regarding the protocol development. I want to go a bit more in detail on the challenges and mitigation. So normally, we have, again, a minimum level of understanding of the disease and the different treatment options. Also, the health authorities for some well-known diseases they have guidelines, and we know, again, what is expected. In COVID-19, this is different. So there are new sites in the disease coming in on a continuous basis, and that has an impact on -- for example, in an exclusion criteria, but also on the stratification factors. These new insights are also at the side of the standard of care. For example, there was the case with dexamethasone, which was -- seemed to be beneficial in the U.K. trial, at least that led to the implementation of dexamethasone as a standard of care in U.K. So you need to be flexible somehow based on different insights. Different health authorities have also given contradicting sometimes opinions. And you want to reduce the burden at the site level. So that -- you want to align as much as possible standard of care assessment in the best way possible. So -- because it can be a challenge that if you request too many procedures from a site that they are no longer interested or they cannot participate. That's not feasible in terms of workload for the site. So as a mitigation, what we have done at SGS is we ranked the priorities of the assessments, to have also input from different experts in the field also across different countries because there is also a change between different countries, but -- I mean, difference between the different countries. You need to act agile when new information becomes available. And it's best to not restrict concomitant mitigations too much so to allow the best standard of care that's very important for ethics committees. What also is very important is that you have a highly experienced study team, including statisticians and medical writers because we have seen that authorities have clear focus on the end point analysis and as well as the interim analysis. And medical writers as well, of course, they are important because with this very short turnaround time lines, there can be multiple protocol amendments. And it's important that this can be written in short time lines and still allowing sufficient time for protocol quality checks. Lastly, you could also work with country-specific versions of a protocol. If, for example, one of the authorities is very restrictive, but you don't want to have this implemented across the whole study, you can, for example, change some of the in- or exclusion criteria. Of course, you need to think about the bigger picture and the impact that might have on your end points. Next topic I want to discuss with you is the site selection and activation. So as for a standard process, decision-making is done after completion of the process or at least after partial completion of the process. For example, if you want to select some site, it can be an advantage that you first have a look at which site and what is their geographic distribution across the country and which sites are interested and are capable to run the study. Also, our preferred option is to go on-site for a site qualification and as well for a site initiation visit. And for the SIV, we prefer to have all study supplies available so that we can do a check of the good receipt of -- for example, lab kits and IMP. The challenge with COVID-19 studies is that sites themselves they need to rethink how they will conduct a study because they sometimes work with COVID-19 wards. So they need to see how the study staff will be able to do all required study procedures working in this high-contained environment. Sometimes, while a lot of people are working remotely, so not only the study staff, but also at sponsor site or at the CRO site, so at SGS site. So it can be difficult to establish a real relationship with sites. And also training of site staff, it can be a bit more difficult, if working remotely. Then for site activation. Since there can be multiple protocol versions, some sites can be activated under different protocol versions from one site to the other one. So that can be a challenge to keep the oversight. So as a mitigation for this fast start-up, we have started site activation activities at risk. So that means even if we don't know that a site will be -- in the end, will be selected or be initiated, we already provided them with the templates and draft contracts, for example, or a study budget so that at least these activities can already start. Also for example, we have seen some countries like U.K. and France, they have a template contract in place, which is very useful because it's one contract for all sites that will participate in that particular country. Another mitigation is, of course, remote visits. So not going on site, but we do a remote SQV visit. There we still focus on trying to have the highest possible quality. So for example, we work with videoconferencing to still have a look at all the facilities that are available at that particular site. [Audio Gap] I want to discuss today is the study setup itself. So the standard normally in other -- any other different setting we have a stable protocol available for site selection, but also for the EDC or the electronic data capturing system development. The challenge here is that we have multiple protocol amendments that are triggered not only by the authorities, but also by investigators or competing trials or new insights that come around. And this fast health authority approvals that we have seen are clearly beneficial, but it also has an impact or it brings a challenge for the back-end systems because they need to be ready as well in a very short time line. So the mitigation, what we have implemented there is even more items that we track. And so to really keep the overview of the different protocol version, of the different requirements in each of the sites or countries, what we have also been discussing is implementing paper CRF at the start of the study. So it's not that we would shift from an electronic data capturing system to paper CRF, but it could help to already collect data before the EDC system would go live. So it would be a temporary solution for -- to capture all required data. And the other mitigation is, of course, mid-study updates of the EDC system, and that was then fast tracked so that we can rapidly implement any changes, for example, in eligibility criteria or extra assessments that were required as per protocol. I would like to go with that quote and a picture that demonstrates the clear needs for flexibility of setting up and running COVID-19 studies. So the quote, "The secret of change is to focus all your energy not on fighting the old, but on building the new." You clearly need to be agile and flexible to set up this COVID-19 studies. And it's not only your own procedures, but you also need to collect as much information as possible from the outside, from competing trials, from changes in the environment to make sure that the study you're setting up is -- the setup is done fast and you can still deliver quality. And that's our agenda, and I'm happy to take any questions you might have.

Thank you, Dominiek, for this very interesting presentation. Let's see if we already have some questions coming in now. Yes, I can see there's already a question. Are there any countries that stand out in terms of regulatory approval and setup?

Well, so indeed, you see that every country in fact wants to be as attractive as they can be to run clinical trials, and some have been more adaptive to the COVID-19 situation. So for example, and indeed, what I also mentioned during my presentation, for Belgium, for example, there was a very fast approval process. So they really shortened their time lines to around 10 days to already get feedback on initial submission, which is really substantially shorter than in a normal trial where you have around 1 month to receive feedback. So definitely, Belgium was there kind of outstanding compared to other countries. If you see then, for example, other countries work with contra -- unique. So that, for example, in France, we have it -- or in U.K. as well so that's also shortened the discussions with sites. So it's not that one country stands out, but still doesn't know what is a good example in fact on how adaptive they were to the situation.

Okay. Thank you. We already have another question. Do you think some of the mitigations will last past -- post-COVID-19?

I think that monitoring will really change in fact after the COVID-19 situation has, hopefully, resolved, let's say. Because I mean we also at SGS have been moving more to remote visits. It's not only because -- yes, at mandatory sites where we're choosing to have monitors on site. But we also see clearly advantages as well. I mean it's sometimes easier to set up these visits. I think also access to patient data somehow that will need to change a bit. I mean Europe has been -- or is still very firm on that also now with the data protection regulation that is in place. But you see that then you get issues, for example, if you have these situations that monitors cannot go on site and you cannot do SDV, and that's not -- I think that will have to change in the past -- or they will need to find solutions to still access this data, but of course, in a securer way. So for example, we see in U.S., they have more access to the electronic medical records since so long.

Okay. Thank you. There's another question. How many amendments did you face? And were the regulatory authorities fast in terms of assessing the amendments?

So in terms of assessing the amendments, indeed, so that -- we saw that they clearly prioritized these COVID-19 studies. So indeed, we received impact within weeks -- well, within 1 week of the submission of the amendments. And what was the first question? How many number of amendments?

Yes. How many amendments did we face?

Well, of course, that depends from study to study. But I can say it's quite substantial, honestly. There is really one amendment per country you're participating in, so that at least. And the issue is, of course, if you have an amendment, in particular provided by country A, you also need to submit it in country B, so that can again trigger another amendment. So it's somehow a vicious circle, and that's why I would really go for parallel submissions where at least you can combine feedback that you get from authorities.

Yes. Okay. Thank you very much. We have time for another question. Did you experience challenges with international trial as compared to European limited trials at site and at health authority level?

I did not see a clear difference with running trials only in Europe or if you ask, for example, the States or we also have a study with -- that is also running in Brazil. It's very similar, honestly. But what -- again, what you need to think about is that that's, I think, in general, for global Phase III trials, you need to make sure that your study assessments that you are requesting that it's feasible for almost all sites. So don't focus specifically on only tests that are being done in Europe. You really need to think about the bigger picture to make sure that we can collect all data from all patients, irrespective in which country they are enrolled.

Okay. Okay. Thank you very much. Maybe another question. Because of the lockdown in various countries, how did sites ensure patient visits for the end point evaluation visits, like imaging assessment, labs, et cetera, critically, which cannot be done at home or by means -- or by other means?

Well, so far, the studies that I have been managing, there were no home -- well, all visits have been done so far. So we have one inpatient study. So that's obvious that visits can be done. For another study, patients have to come to the hospital, but that was still feasible. So, so far, yes, we don't have studies that -- I mean, that the patients had to stop their treatment. What has happened is that the studies were put on hold so that recruitment had to be stopped for a particular study that they could just not enroll any additional patients because the site had to focus on treating COVID-19 patients, which I think is obvious and understandable.

Okay. Thank you. Maybe we have time for one last question. Do you know of trials needed to terminate early due to the competitive environment?

Yes. Well -- terminate, I don't know, but we were informed about some sites that participated in some of the studies we have been running that they stopped the setup of other competing studies. So I don't think it's really termination, but it's before the first patient was enrolled that eventually they stopped. And I think that there's some way -- or you could see this, in fact, it was in Europe with the second wave that was -- the first wave, sorry, that, that ended. So in summer, there was a decrease in cases. And then you saw as well that some studies stopped virtually in the initiation phase. That was also something that we were always focusing on is we knew or we were expecting a second and probably also a third wave. So you really need to think a little longer term to make sure that your sites are ready to enroll patients once there would be again a peak in COVID-19 cases.

Okay. Perfect. Thank you very much. I think we're running out of time now, unfortunately. So Dominiek, thank you again for your presentation and for answering those questions. And thank you to everybody who was attending.

Okay. Thank you. Have a nice day.