Why Rapid Patient Recruitment is the Ticket to Successful Multinational Trials

This week on The Totally Clinical podcast, I am joined by Peter gray, chairman of the board of tekrar.

Peter has an extensive 40-year career history, working at a senior executive level, including 30 years in the pharmaceutical services industry, and ex-ceo of icon Peter has a deep understanding of the challenges of the clinical trial industry. During this podcast, we discuss why COVID has been good for clinical trials, the challenges of clinical research in major hospitals and academic research centers. Why decentralized trials are not necessarily the panacea some people believe them to be, and how a Warning letter from the FDA prompted him to passionately engage with tech.

Thank you so much for joining me today, Peter. You have been involved with tech growth since the company's inception, and there's quite a story behind why you initially thought you were behind, why you were initially inspired to join tech grow. Could you elaborate on this? Thanks, Hannah.

Good afternoon. Yes I'm a great believer that often are our best lessons are learn from failure. And as you alluded to in your introduction, there are the failure that I learned a lot from was a Warning letter from the FDA,

probably about 14 years ago, where it

arose from a investigator site that had not conducted the procedures in a trial appropriately, particularly in relation to the handling of a complex study drug. The net result was that the patients recruited at that site or excluded from the study analysis, which had some very significant consequences.

Arising from that experience, we did a complete review of our air quality control and quality assurance processes. And one of the outcomes of that review. Was the identification of a company that had developed tools for training investigator sites on GCP and on the specific procedures for given clinical trials, and had a tool that was available to the sites during the trial to instruct them on the procedures that needed to be conducted on a day by day patient visit by patient visit basis. And we acquired that company re-implemented, it's its tools across our organization with the goal of enhancing quality and ensuring that quality at sites and in our own in our own operations would be as good as they possibly could be.

Road forward. Eight or nine years and I've left, I kind of retired and the founders of that original company have founded a new company using today's technology, smartphones and so on to take the idea behind that original concept. Several steps further. And obviously, the lesson that I learned from the trauma of a Warning letter was still deep in my psyche.

And when they approached me to ask me what I, what I chair tackle as it was, as they had named it, I was an enthusiastic participant because again, I so profoundly believe that quality is essential in clinical research. And yet making clinical research as accessible as possible for investigators, investigative sites and patients is an essential for the Advancement of human health. And that's where I see tech roles being placed. It's a very unique set of tools that can only enhance the quality and the ease of participation for sites in clinical research and the quality of how they do that.

That's quite a story you have there, I imagine that after many years of experience working in the industry, you must have things that have stood out to you in terms of industry changes you've seen during your career. I mean, you yeah, you make me feel old now, and I think about that because it goes back a long way, but I could say that there's so many things that have changed in the clinical research sphere in my time in the industry. And since I left the industry. And globalization was only just beginning.

So the conduct of multinational clinical trials was a fairly new concept. When I first joined the industry, outsourcing by pharma companies of the conduct of clinical trials was again in its infancy.

And trials were less complex than they are today, so the complexity of trials has increased incredibly significantly over the last 30 years. The most of the trials that were done back then were for small molecules.

Biologics are now the dominant feature of clinical research. Oncology and rare diseases were rare beasts in clinical research at that time. They now dominate how the trials that are conducted. That's where all the focus is these days.

And, of course, technology was little used, it was the industry was totally paper based. And even though

in the year 2000, 1999, 2000 during what was then called the boom, there were great predictions of how technology would transform the industry. It has taken COVID 19 to actually push the industry to adopt technology to a much greater extent. And I think we are truly seeing the impact of technology in the industry today, where it has only been talked about over the previous 20 or 30 years.

So there's been a lot of change and all of it making clinical research much more interesting, but also much more complex, which is why tools such as tech are so essential. You mentioned the COVID 19 pandemic, and despite the horrors and disruption that it wrought, you do believe it's been a positive for clinical research. Why is this? I think there are several layers of answer to that question.

First of all, one of the great benefits is it has made the general population much more aware of the need for

and the importance of clinical research. We we were getting news reports on a regular basis about when vaccines might be available, and we started out with people being skeptical as to how quickly the predictions. How how optimistic the predictions were in relation to how quickly vaccines would be available. And then we were getting updates about the progress of different products in the clinical research arena.

So the general population became aware of how important trials are. They were aware of how long they take and that increase in an awareness, I think, is a real positive in the long term in helping people to understand why clinical research is conducted and hopefully encouraging more people to be willing to participate in clinical research, recognizing that it is a huge plus and a huge benefit to the enhancement of human health. Another

factor, another layer was that vaccine skepticism, which was obviously widespread and remains widespread, highlighted the importance of robust, high quality, scientifically validated data.

The number of conversations I had with people who I believe to be pretty sophisticated, who said, oh, I wouldn't be sure but about having that vaccine. I don't really know what you know, where it's come from, and I don't really know what's in it. And my response used to be, well, you take aspirin. Do you do you take paracetamol?

Do you know where that comes? You know what's in that? Do you understand that? And the response was that they trusted those things because they've been around for a long time.

We, the skeptics, force us in the industry to recognize that we need to not only produce valid data, but to make sure that we can articulate the work that we've done, the reasons why it's done and the robustness of the data that we are delivering. So again, it's raised awareness in the human population and the general population of clinical research, and it's raised awareness of how scientific method is so important as a background to the conduct of that research. And the third aspect that I think is important is the people became aware of how important it is for rapid enrollment

and the need for results in clinical trials.

And one of the side effects of COVID was it's slowed down clinical trials. In other indications. For example, in important oncology trials, they were delayed because patients were not able to get to their physicians or to their hospitals. And so the progress of clinical research in general was slowed.

And so the and I got I got a pause, and I want to start that third point again because I'm going round in circles, ok? Yeah, of course, of course. And let me just rethink my point here. Yes, OK, so starting on the third point again.

So a third important area. Was the pandemic illustrated how important the conduct of clinical research is, and particularly the rapid conduct of clinical research? Or for non vaccine trials. There were a lot of delays caused by the fact that old processes did not lend themselves to patients continuing in trials when they could not visit their doctors, when they couldn't get into hospitals and so on.

And that heightened people's recognition that we needed to use technology to overcome the barriers that COVID is causing. So whether it was telemedicine, whether it was remote monitoring of investigator sites and our various other technological, not particularly advanced technological tools, but technological tools that could be used to overcome the barriers that COVID was creating has led to the industry's mind being opened up to the use of technology and the recognition that clinical research can be conducted in a more efficient, less paper based way and has heretofore been the case. That's

a huge positive because I think it will accelerate the conduct of trials. I think it will also make it easier for patients to participate in trials in the future. And I think it will also make it easier for investigators and investigator sites to participate in trials in the future. So COVID obviously has been very disruptive to our lives.

What has brought a number of positives in the arena of clinical research and the advancement of human health? Yes, the pandemic has certainly put technology on the map industry wise. Now I know that you have traveled considerably and witness how witnessed how trials operate all over the world. Are there any insights that particularly stand out for you?

And if so, why? And I think I'll give you an anecdote of one particular visit I made. But about 15 years ago to a major hospital in Eastern Europe. And this was a former Soviet era hospital where under their great centralized planning at the hospitalized, the hospital specialized in only one disease, and all of the patients with that disease came from hundreds of miles around to be treated there.

As a result, for sponsors, the hospital was a very attractive location for clinical trials in that specialty. For the hospital, participation in clinical trials was a great incremental revenue source in what was an underfunded health system. While for patients in that country, access to free care and modern medicines was a strong incentive for participation. The net result was a very large number of trials being conducted simultaneously in that hospital.

And when I visited, I recall the clinical study Coordination Center being a very large room filled with bookshelves on which rested hundreds of lever arch files representing the study documents for multiple sites. And I was struck by the impossibility for the study nurses or investigators being able to know all of the detail of each trial and the likelihood of errors either in procedures are in the inclusion or exclusion criteria decisions. And at the time, I didn't have a solution, but I could see the problem. If I then roll you forward 12 years and one of tomorrow's investors.

Was once an investigator in a major US East Coast academic Research Center. He speaks with passion about encountering the very same challenges, challenges in the u.s., multiple trials being conducted in the hospital and treating physicians needing to know in the moments that they're with the patient what trials were ongoing at the hospital and what the inclusion or exclusion criteria were or what procedures were to be conducted on patient on that visit. His fund was a very early investor in tech grow, as he passionately believes that techno solves that challenge.

So you have to go back to your question and. I've witnessed how trials operate around the world, and we are. Everyone wants as many sites as possible to participate in trials, because that way, clinical trials will be conducted faster and that way, better medicines and treatments for diseases that aren't currently treated will be brought to market faster. So more sites

and more patients participating in trials has a very substantial knock on benefit again in human health.

So finding ways of having more sites participate in trials and finding ways of eliminating errors that they might make are finding ways of eliminating it, being easier for the doctor to say, I don't know whether this patient will fit in this trial or not. I haven't got time to go and check, so I won't enroll them in this study. Those those, those are the challenges of getting patients into clinical trials, and anything we can do to alleviate those challenges is a positive. And again, that's where I believe tacrolimus can be a great boon to the conduct of clinical research because at the physician's fingertips is the information he or she needs in the moment that a patient sits in front of them in order to make the right decisions.

So from what you were saying just there, it seems like this really is an international issue. If we think of the example of the Eastern European hospital earlier, this is just a small illustration of the globalization of clinical research. Are there any particular challenges to multinational trials and do current geopolitical events threaten what has been what threaten what has been developed over the last 30 years? I guess following on what I said earlier, you know, the Holy Grail of clinical research is rapid, high quality, patient recruitment.

That is what drove globalization initially, then came

orphan drugs, which by their nature, have much fewer potential patients, which necessitates spreading the recruitment net much wider. The sorry, I got to pause there. Because I've lost my note. Here we go.

Sorry, sorry. No problem. OK, there that I can just continue on. Of course, you know, we can do a lot of editing or we can do as much editing as we need to do so.

Yeah, of course. OK, so I finished with spreading the recruitment net much wider. As a result, multinational studies are here to stay. Geopolitics may alter some of the locations that are used, and God knows we know that today.

That will only drive more activity in other regions because the quest for patience, for the quest for the right. Patience in a particular disease will go on and on. And the locusts are the focus of location may change, but the search for locations will not, will not. Again, technology will be a very important enabler of this, and technology has the potential of being the leading are leading and able.

Think about it, if you're an investigator in Eastern Europe or in Asia or in South America, having the protocol literally at your fingertips. And being able to communicate instantly with the Sierra are the medical staff of the sponsor relating to your queries or clarifications. It just makes it so much easier to participate in a clinical trial, much easier to adhere to the protocol, and it becomes much more

likely having that experience that you will do so again and again, which means you become an experienced site that sponsors and CEOs can rely on in the future. And one of the challenges of globalization is that a lot of the investigators participating in trials English is not their native language and yet a lot of clinical research and most protocols in clinical trials are written in English.

Having a tool like tekrar, where you can search for the right section of the protocol and get the answer on your smartphone in a moment, you are able to send a question. Not again, not in your native language. So you've got the time to compose the question. And then when you get the answer back, you've got the time to absorb what it means.

Those those are. Maybe it seems obvious. Maybe it seems a bc ish, but they are challenges that every investigator faces. And I always go back to the point that investigators aren't participating in clinical trials because they want to participate in the clinical trial.

They're participating in clinical trials because they're treating patients and they want the very best for their patients, and they've identified that particular patients of theirs will benefit from a potential new treatment. So what they want is they're sitting in front of this patient

who they're trying to care for. They don't want to be rustling around in a lever arch file. They don't want to be going to their computer and looking up things and having the patient waiting there patiently for 10 minutes while they find they find an answer.

But but doing something quickly on their smartphone, and I'm getting the answer that they need rapidly as the patient sits in front of them just makes their lives easier, makes the patients experience better in general, makes the conduct of the trial seamless with what is the primary issue, which is the treatment of patient? And that is for me, the key. Now on to a bit of a different topic, sustainability isn't necessarily a word that one immediately associates with clinical trials. But if we think about how technology is enabling the shift towards paperless trials and also streamlining resources, we can see how the industry is moving in a greener direction.

What are your thoughts on this? Again, I think technology enables this, and therefore. Uncovered may have created an impetus to the adoption of technology in an industry that has always been very conservative. I think the Green agenda will also create pressure for the use of technology to reduce the carbon

footprint if I can use the cliche.

Using technology for telemedicine, for consultations with patients when you don't meet the patient to be in New York, the doctor doesn't need the patient to be in their office when the monitor doesn't need to go to the doctors site every time, but can again using technology, whether whether, whether it's macro or whether just video conferencing can conduct the procedures they need to conduct on a monitoring visit remotely. There are so many different ways in which technology can reduce the burden on the environment that clinical trials can cause. If you if you use the old methodology paper people traveling backwards and forwards all the time to do everything, I'm visiting every site, all of the time on unnecessary.

If you use technology and you use analysis, data analysis and various other tools that facilitate infrequent, it doesn't eliminate the need for people to visit or to go to a location from time to time. But the frequency with which that is required can certainly be massively reduced. I think that would be the most important impact that technology can have, where we can all contribute again to an imperative for our planet, which is to reduce our carbon footprint. Yeah, fewer Sierra's flying around everyone.

So if you and fewer patients have to travel to see their physicians for visits that are only mandated by the clinical trial rather than by their treatment regime. Exactly so if we consider the future of trials, what current trends do you see continuing and which do you see fading away? Get your crystal ball out. I think there's certainly a lot of talk at the moment about decentralized

clinical trials and as it's extreme.

People seem to imagine a world where sites are no longer necessary and patients can be participate in clinical trials remotely. I'm not sure if that's happening in any instance today. And if it is, I suspect it's very rare. So, so I'm not sure about trends that are fading away, but what the talk trend of that, I think will fade away because the reality of clinical research is, as I said earlier, doctors are treating patients for illnesses.

And doctors need to see their patients, not maybe every single time the doctors need to see their patients in order to treat them adequately in order to understand the progression of their condition and to understand how psychologically they are managing in the environment that they're in. So one of the trends that I think will diminish is the talk of decentralized trials. I think the likely future is of a hybrid model, maybe a little like I spoke about. In relation to the conduct of clinical trials themselves.

Visits will still be needed, but they may be less frequent, and therefore the hybrid model will be whether some remote care delivery and some remote consultation and some remote delivery of data by the patients. But there will continue to be a need for involvement by investigator physicians, and there will continue to be a need for some element of site visits by the patient to the investigator said. And other trends that I think that might fade away. I'm not sure that any of the things that I've talked about will fade away if I go back to an earlier question, you asked me, what are the things that have developed in the industry, in my time in the industry and I talked about globalization, the complexity of trials and oncology and rare diseases becoming much more significant and biologics and technology, all of those things have emerged and have become much bigger factors in the industry in the last 20 or 30 years.

And I don't see them going away, if anything. Gene therapies bring a greater level of complexity. excuse me, I hope we can edit that out. If anything, gene therapies bring a greater level of complexity.

And will bring new challenges in the future that I can't even predict today as to what they will, what they will mean for clinical research and what effects they'll have on health care. So, yeah, in terms of the next question, I feel you've answered that, but what I would like to ask is what the signs are when we are able to establish that a trend is not simply passing and is here for the long term. If you feel that's a decent question to ask, like, you know, in terms of things you've seen that indicate this, this, you know how that. So maybe I'd phrased the question like, how do when a trend is not simply passing and it's here for the long term?

What are the signs? Sir, I know the answer to the question how? Yeah, if you don't, that's fine. I just think I just think it's quite interesting.

If there are specific. Yeah, I guess it was more about digging into some. Maybe an anecdote or an idea. You might have had in terms of things you've seen before that where you've written that this wasn't going to last or you thought, well, that is, you know, some maybe drawing on your experience.

Here's here's the thought, and this may substitute for the last question. So you know, you let it this and you might use one, not the other. I was at a board meeting earlier today where. We as a board were meeting for the first time in over a year.

Face to face and we were talking about the changes in work practices that have emerged again as a result of COVID. And there were different views around the table about whether remote working is here to stay or whether a hybrid is going to be the model for the future, or whether in time remote working will become less and less acceptable both for employees and employers, and will be back to much more a model, much closer to where we were before COVID in terms of people going to the office. We're quite different views on that. What a theme that came out in everyone's comments was that.

A totally remote working model. Was leading to higher staff turnover and leading to challenges in maintaining a company culture and having people feel a part of something as opposed to a job that they log into every day. And so the conversation came around to a recognition that there's a really important part of relationships at work that are to do with personal contact and the need for people to actually have personal interaction, face to face interaction, to make them feel truly a part of an organization, a part of something that they want to be a part of. If I take that analogy to clinical research.

And I think that. The aspiration that more and more clinical research can be done remotely on a decentralized model or whatever one cares to call it. And I think the same factors apply to that. How do you get patients to feel as if they're getting at the right level of care, if that care is being delivered to them remotely?

One of our experiences as globalization developed in clinical research was in less developed countries. Our patient recruitment numbers were much, much greater, much, much better than in developed economies, simply because patients were given access to more medical care when they participated in the clinical trial, which was not something they had access to in their less developed economy, health system, whatever, whatever you care to cause. So there's an appeal to participating in clinical research that is partly driven by the greater level of attention you're getting from your physician when you participate in the clinical trial.

If we try to move to a remote model, we lose one of the things that actually attracts people to participate in clinical research and that, I think would be detrimental. So I believe the push towards finding more ways of running trials on a remote basis will founder on the rock of let less incentive for patients to participate in trials in those circumstances. And that's a trend, therefore, that I think will. We perhaps change and may indeed disappear in the next two or three years.

And it was that coherent. No, it was definitely and I actually I agree, I agree with that. I think that it's really important to work with people face to face at least part of the time and then you apply that to trials as well. So staying on the topic of the future, do you have any thoughts on crows and their business models and how do you see them changing, if at all?

I think earlier I referred to the fact that when I joined the industry, outsourcing to CEOs was in its infancy. And obviously, that has changed dramatically over the last 20 or 30 years. And zeros are now an integral part of the ecosystem of the pharmaceutical industry and clinical research in particular. again, because of the conservatism of the industry, the business model of crows has been slow to evolve, as was the business model of the pharma companies before them in the conduct of clinical research.

That wasn't because there was an inertia among the industry or among CEOs. I think it was largely driven by a conservatism at the regulatory level that made pharma companies and therefore their agents, the crows very reluctant to seek to be innovative in the way in which clinical trials were conducted, simply because the risk was that the data would not be accepted by the regulatory agencies if, if not, if not collected in the conventional way. So CRL, whose business models need to change as regulators perception of what is appropriate in the conduct of clinical research needs to change. And

again, we're circling back to covid, but COVID has given an impetus to regulations to see the things can be done differently and need to be done differently in order to advance human health. And as a result, I think serious business models will change. And now it's a case of who's going to be the more enthusiastic the regulators are, are the crows stroke pharma industry. I think the door has been opened to try an innovative approaches.

I think the door has been opened to conducting clinical research in more creative ways. And at the same time. The technology exists to assuage the fears of regulators that quality has been compromised in that scenario. And therefore, I think the industry will change in the years ahead.

business models will alter and that change and that alteration will be enabled and driven by technology to a large extent, tempered by the conservatism or other lines of the regulatory agencies. So we thought we've touched on a lot of topics here, which is great, I think maybe this would be 2 podcasts, a series. Yeah, that could work. You have to listen back to it and see if a lot of it is waffle.

I feel I've been lost. It's really good to go deeper than we normally do. And you know, we want to start doing more of that because we, you know, we have great guests and we want to make sure we do more of that. But in terms of the chairman of the board, the excited in terms of the company's trajectory, I think maybe we should finish with that question.

I mean, in terms of anything else you'd like to add. You have mentioned that I think apart from directly tech grows insights part. Because I think that might be better being moved into another section. Yeah, I wouldn't mind.

Why don't we record that question anyway? You can see, does it fit in or not? Because I'd like to get this 30% of sites failed. Yes Yes.

You know, I wouldn't put it at the end, though. I don't think I put it further up in another section, and I'll definitely add in questions. I have. I mean, yeah, there'll be quite a lot of editing on this because there's a lot of information, which is really good.

So and finally, as chairman of the board of tech crew, what are you most excited about in terms of the company's trajectory? Going back to an earlier question and you ask me why, why did I get involved with tech crime? I was excited at the very outset by the fact that here was a solution using the ubiquitous smartphone to make physician patient sponsor interactions as seamless as possible. And earlier, I alluded to the fact that doctors don't want to be playing with technology when there are treated, when they're treating patients.

They want to be treating patients. And so let the less intrusive technology is into the patient physician relationship, the better. What I'm excited about in tech role is because we all are used to having smartphones in our hands because patients are used to seeing everybody with a smartphone in their hands. If their doctor happens to be sitting with them and has a smartphone and is just tapping something into the smartphone as he's talking to the patient.

That is not going to be unsettling for the patient in the same way as if the doctor of swiveled around in his chair looked at his computer screen and tapped on a keyboard and then swivel it back to the patient would be intrusive to the patient doctor relationship. So I would think what Takao is doing and what techno has done is enabled. The physician. To ensure that they're doing the right things, be able to ask the right questions to be able to gather the right information.

And at the same time, concentrate on their primary task, which is to treat the patient who's sitting in front of them at that given moment. But for the. That's from the physician perspective. Meanwhile, in the background for the sponsor of the clinical trial, having the comfort of knowing that every physician participating in the trial or every study nurse participating in the trial of every secre who's overseeing a monitoring trial has at their fingertips all of the information about the trial and how it should be conducted at any moment in time.

And if there's a question that can't be answered from the study documents that are available at their fingertips that they can rapidly get that answer from the CRA or from the medical staff at the sponsor, that's hugely powerful and that isn't available anywhere else. And it's a unique capability that I believe, will help to transform clinical research, will help to open up more physician sites and help to accelerate patient recruitment. And at the same time will ensure that the data that is delivered is of the highest quality. Is there anything else you'd like to add?

I think one last plug for tech role, if I could. One of the features of clinical trials that for years and years and years has been despite the best efforts of industry, best efforts of feasibility studies before the study starts. 30% of investigator sites give or take fail to recruit a patient in a given clinical trial, so one goes to all of the expense of identifying sites who apparently have the right patients investing in getting regulatory approval for that site, getting ethics committee, approval for that site, etc., etc.,

et cetera and you set up the site and then they don't recruit a patient. Monitors have to visit them. So there's an enormous expense involved in putting sites in place. And if they don't recruit a patient, then your return on investment is zero.

And in fact, it's negative. tackle. Is a tool whereby immediately you get a sense of and the sponsor gets a sense of whether that site is engaged in the trial, if they never turn on tech and never look at it from the moment that they're given access to tackle. And that says, is this site really interested in this trial?

If they are recruiting patients, what they are not querying the protocol are the documents on tetro. Does that raise a question about is this site actually doing a quality job? Are they are they conducting the correct procedures? So the signals the tecra gives in relation to a site's engagement with the trial come from the very first moment that they are given access to tetro.

And if they're not going to recruit patients, you're going to see very quickly that this site doesn't seem to be engaged and therefore you can make a change. Therefore, you can accelerate the trajectory of your trial by wrapping them out and bringing in other sites instead are changing the focus or motivating them more or whatever steps you need to take a one to take to change that trajectory. I think the access to real time, immediate day by day data as to what a site is doing and whether the site is engaged with the trial is enormously powerful and has the potential to accelerate trial completion and reduce cost.