Trials with Maya Z

Hello, everyone, and welcome to Trials with Maya Z. It's Maya again, and I'm super excited today. But this time I have a surprise for you. I'm here with Till Bruckner, the founder of TranspariMED, a very interesting organization. And today we're going to speak about something that you don't, I'm pretty sure you don't even expect.

Teal. I want to give you the words to introduce yourself because I was absolutely amazed by your background and what led you to clinical trials. Giving the word to you too.

Yeah, hi. I'm a political scientist by background, actually. I don't know anything about medicine. Um, six years ago, I didn't know anything about clinical trials. And then I heard that many clinical trial results are never made public. And I thought, how can that be okay? Isn't that a complete waste of money?

This doesn't make any sense. So, I read up on it more and I thought Well, you know, this is impossible. We've got to change that. We've got to do something about that. So I started up TranspariMED and I've been talking about clinical trial transparency ever since.

So you started TranspariMED six years ago. Is that right?

Yeah, that's right. Six years ago, it's been.

Okay. So can you tell me more about TranspariMED as an organization? You mentioned transparency is at the core of your organization. What exactly are you trying to do and how are you achieving this transparency in clinical trials?

Okay, so you get billions of dollars invested in clinical trials, you get millions of patients participating, you get tens of thousands of scientists like doing a fantastic job at designing and running these studies, and then a lot of them never are made public in the end. You simply don't know. Was the trial outcome positive? Was the trial outcome negative? What benefits were detected? What harms were detected? And it's a complete waste of time and effort. So, with transparent, what we're trying to do is we're trying to raise awareness about that, of course, but we're trying to design solutions. That is really the focus.

We're not saying, oh, this is terrible. This is a problem. We're saying, okay, here are a few solutions that you can use here solutions that you can use as a university, as a medical research funder, as a policymaker, to end this waste of public money to end this complete unnecessary waste of medical insights, scientific insights, that's not how science is supposed to work.

Science is supposed to progress from one study to the next. It's not meant to progress from one study, and then there's an invisible study that nobody learns anything from. And then you repeat that invisible study again, because you didn't even know that somebody else did that invisible study.

It doesn't work for patients. It doesn't work for taxpayers. And it doesn't work for researchers. I mean, I can't imagine anything more frustrating than spending two years of your life working on a clinical trial and need to find out that somebody else a few years ago already found out that the treatment that he investigating didn't work. That is not what researchers want to be doing with their lives.

So, we're trying to move forward to a world where every single clinical trial result is reported.

That's interesting, Till. And I have like three different questions that are regarding what you just said. But starting, you mentioned public money. And in the clinical research space, we have clinical trials indeed funded by public money, but also we have a lot of clinical trials funded by commercial money.

So do you think there should be a difference between how transparent we are? Depending on whether this is a public clinical trial, publicly funded clinical trial, or commercially funded clinical trial?

A lot of other people have thought about that question, and you get the World Medical Association, which sets out standards for ethics and medical research worldwide. In the Declaration of Helsinki, they've very clearly said that every single clinical trial has to be registered and the results have to be made public without exception. So, it doesn't matter whether this is an industry trial or a publicly funded trial, or just a small trial that an investigator somewhere decides to do without outside support that happens as well. And then you get the World Health Organization, which also says that every single clinical trial should be registered and the results reported.

So from that perspective, there's absolutely no difference. If you've got a publicly funded trial, you're also wasting taxpayers money. But in industry trial, all your patients are volunteers as well. They make the investment of their time, they offer their bodies for medical research in effect, and you have a very clear ethical and scientific duty towards them to make the results public.

So I don't, I don't think that's controversial if you're a pharma company and you run a clinical trial.

hmm.

You do not own the results 100 percent. You do not have the ethical capacity to decide. Oh, I don't like the results. I'm not going to make it public. And in many countries, also, you are legally obliged to make the results public.

And that's an increasing trend we're seeing.

Okay. So what is the level of transparency that we currently face in the industry, Till? What's the status quo today?

Wow, that's a difficult question. Generally speaking, what you see in industry is that large and well organized pharma companies, they follow the law. So if the law says you have to make your clinical trial results public for these types of trials within one year, large pharma companies do that.

They're excellent at that actually. I often go to academia and I point to large pharma companies and I say, Look, these people are following the law 100%. It's the law. You should be doing the same. It's clearly possible to do. There are two gaps there. The one is smaller pharmaceutical companies, which might not have the sort of regulatory staff and expertise, who sometimes don't follow the law simply because they don't fully understand the law or because they don't have good oversight over their portfolios.

And, the other gap, which is, larger is that for many clinical trials in many jurisdictions, there still are no such laws requiring the results to be made public. So, the company can look at the results and they can say, Oh, that's not the result that we were hoping for. We'll just decide not to make it public.

Hmm.

And, I think from a commercial perspective, that's completely understandable, from an ethical and scientific perspective, it's a massive scandal, but, if a company does something that is clearly unethical, but that is legal, technically speaking, I wouldn't put the blame with the company in the first place.

I'd put the blame with the lawmakers and the government. Why do you allow this to continue? Because if you've got profit maximizing companies, I think you can expect them to try and maximize profits. It's really up for governments to set out clear rules for this and then force clear rules.

That's very interesting what you're mentioning. Should I understand, because you mentioned the World Medical Association and they created these laws that actually demand that you to register trials and also report the results. But from what you're now saying, not in every country, if I understand correctly, not every country, these laws are being applied.

So is that something that countries decide independently? And are there any institutions, like, for example, I'm originally from Bulgaria. Honestly, I have no idea which will be the institution here that will decide if clinical trials should be registered and their trial results should be reported. But honestly, I spent quite some time in the UK working for the NIHR as well.

And still, I don't recall any institution that actually works on these, on such regulations. Can you give us any idea how does this happen? If the medical, World Medical Association created these guidelines or regulations, let's say, who then is in charge of applying them country by country?

Well, I mean, what the World Medical Association does is it sets out standards and it says those standards apply in every country worldwide. Regardless of national law, there's an ethical standards, but it can't enforce them. It's a bit like United Nations human rights declaration or something like that. Nobody can enforce it.

But if you take Bulgaria as an example, Bulgaria is a member of the European Union and we've now got the clinical trial regulation come into force. So under Bulgarian national law you have to make the results of your drug trial public on a trial registry within 12 months of completing that clinical trial.

That is the national law in Bulgaria. I assume that in Bulgaria, the National Medicines Regulator is tasked with enforcing that law. That is something that has come in all EU countries. And you said, you used to work for NIHR in the UK, and you weren't aware of anything like that there? Well, you know, the world has changed since you work there because, NIHR has got a very clear policy that says that every single clinical trial that they fund has to make the results public.

And if you're an NIHR-funded researcher and you don't make the results public. First of all, they've got a monitoring system So they will notice that you haven't made the result public And then they will send you a very friendly reminder and will say, please, you know we expect you to make the results public you agree to that when we funded you and then they'll send you another friendly reminder and then they'll presumably send you a reminder that's less friendly. And then they'll tell you that you didn't make the results public. So we're never, ever going to give you money again. And we're seeing that from a lot of medical research funders worldwide now who are adopting that starting with the National Institutes of Health in the US, the Wellcome Trust, NIHR in the UK, In some in France, the large funders in Germany, I mean, that has really been a trend amongst the funders.

And it's also been, in all 27 EU countries, we now have national laws like that, covering drug trials and in future medical device trials as well. So, I mean, that's huge progress. The question then is, will the National Regulator actually enforce the law? And we've heard from some regulators, for example, in Denmark, they've been very vocal about it and they said, yes, we are going to monitor this and yes, we are going to impose fines. With other regulators, we're not sure yet whether they're going to enforce the law. For example, in the US, we know that the FDA has had the legal power to enforce a law like this for years and years and years now. And they've been very weak on their enforcement and they've been unwilling to fully enforce this.

But I think in Europe, the picture is different. I think regulators clearly understand this is a problem.

Hmm. But why is that you think that the FDA is not enforcing that more strongly?

That is a huge mystery and at every single conference where people working on trial transparency come together, It's a topic for discussion So you get a law in the United States that says that for many clinical trials you have to pre-register them And you have to make the results public. That law came in the wake of some very prominent pharma scandals around hidden data. And it was passed by an overwhelming majority in Congress.

I think in the Senate, it was passed with 94 to six votes. So, this was something that Democrats and Republicans agreed on 100%. And, then it was signed into law by a Republican president. And then when Joe Biden was vice president under Obama, he promised to enforce the law.

Hmm.

It still hasn't been enforced.

So, um, various campaigning groups, first and foremost amongst the Universities Allied for Essential Medicines, they've been going around Congress now saying this still hasn't happened. So, we've had like Democrats, Senators writing to the FDA and saying, you know, please, we expect you to enforce the law.

You know, the people's representatives passed the law. Why is the agency not enforcing this? We've had Republicans write to the FDA and say, please enforce the law. So, it's absolutely beyond my comprehension why that isn't being enforced. But I think in Europe the tone is very different. And in the US the tone is changing very quickly. We have the National Institutes for Health for years. They said, Oh, we're not enforcing this because the FDA hasn't started enforcing this. And then after the National Institutes of health got a lot of pressure from Congress. They got a lot of pressure from the office of the inspector general.

Suddenly they changed tunes and now they're monitoring this and they're enforcing this, and that's probably going to save American taxpayers, hundreds of millions of dollars going forward every year. It's really going to accelerate science and it's really going to benefit patients. So I don't see any losers in that particular constellation.

Yeah, actually, that's exactly my next question. You're absolutely right.

Conducting redundant clinical research, repeating same mistakes doesn't make sense to anybody. So I wonder who wins from not being transparent with our results?

Well, It depends. I mean, If you're a pharmaceutical or a medical device company and you've already got a product on the market and then you run a clinical trial that shows that product doesn't perform as well as everyone thought it performed if you don't make the results public, then you benefit as a company, very clearly. And patients and the public lose out. But in the academic sector, it's different. Nobody benefits, but it's a collective action problem. So imagine you're a very, very busy academic researcher. So you're teaching at the university, but you're also treating patients at the hospital.

You're writing papers. You're teaching students. You've got an incredibly busy life. You've got 60, 70 hour week, maybe 80 hours. And you're also running a clinical trial on the side. And then the results come in and the results are basically. They're okay, you know, this was a good idea, but it didn't work, and that's what happens in science, you look at things that are very plausible, they're very promising, you get very excited about them.

And then you try them out and you find out, okay, that didn't work, it's a shame everyone was hoping, of course, that the trial would be successful. But, um, sometimes or often it doesn't work. And then you're thinking, oh my god, I am so busy. Should I really be spending, like, two, three days of my time to make the results public when it didn't work anyway?

When no highly ranked journal is going to be interested in my publication. Why should I put the time into it? I don't get the career reward for it. It was a scientific dead end. And the answer is that, well, you know, you should make the results public so that nobody else wastes two years running down that end. So that nobody else runs a clinical trial involving 100 patients who will not benefit from this and It's already known that they won't benefit from this but from your personal perspective at that point It makes complete sense to say, you know, this is not an efficient use of my time. So it's a bit like it's a bit like a Greek tragedy really, where things go terribly wrong, even though the actors aren't necessarily evil. And that's why you need that's why you need like very clear rules in this space.

And that's why you need reminders You know, 90 percent of this problem can be solved if regulators, if research funders just send out a friendly reminder and saying, this is our policy and we expect you to please make the results public now, and then a second reminder. And that's 90 percent of the problem solved.

It's that simple. And then if you get some people who think that, they're above the law, Then sorry, then you'll have to apply the law and you'll have to impose some fines, but that is only a tiny minority because this is not a field populated with evil people. I've haven't met a single evil person in six years of working on this.

And it's one of the great pleasures actually of this work is that, you know, I'm always dealing

actually, yeah, you're absolutely right. Like most people working in the industry are genuinely good people actually. In general, people are good, but then they end up in environments that actually get out from them. Let's say not the best sites, let's say, but in clinical research, a lot of people are incentivized by helping other people, helping their families, helping themselves.

A lot of them are also patients. I met so many people working in the clinical research space exactly because they have a closed one. They were the patient. They went through a hard time. time with their families, friends. I'm also like that. I mean, I started working in the clinical research industry.

Actually, it was a coincidence, but I stayed in the industry exactly because I was struggling with my sister and I realized how important clinical research is for every one of us, it's our future, literally. But going back to what you said. You mentioned pharma companies, they may want to, let's say, not be transparent with their results, because at the end of the day, um, that might damage their commercial results.

So, enforcement makes perfect sense. But thinking about academia, I wonder, do they need the carrots or the sticks here? Like, do they need the enforcement or actually we can incentivize academia by, for example, giving them something instead of, forcing them, like, just reminders? For example, on top of my head, and I'm just giving you this idea to see if that's already available. What if you publish your results, you get more likely to get to the next funding, for example, or that gives you a certain percentage, increase of the funding that you're going to get because you've proved to the system that you're a scientist that contributes to the community by doing research, providing results, and evolving at the end of the day.

So instead of just reminders, can we perhaps use other approaches like giving more funding or encouraging these people to do that? Is there anywhere such a system in place? Yeah.

absolutely. and that's what the World Health Organization recommends.

The World Health Organization says that when funders fund a clinical trial, they should include a budget line for results reporting. So, that if you're applying for a grant to run a clinical trial, you should include a budget line that says, okay, here are four days that I will need to upload the results to clinical trial registry.

And, I want to get paid for those four days of work because that is an integral part of running clinical trials, making the results public. So first of all, it's paying for that. Second of that is when you hand in a grant application to the Wellcome Trust, for example, they will ask you for a list of the previous clinical trials that you've run, and then they might ask where are the results of these trials?

Can we please see them? And if you say, well, I've only made half of them public, then they'll say, sorry, we don't want to invest money, uh, with you because this is not going to benefit patients, you know, you can't guarantee that your research will actually benefit science and patients because you haven't made results public in the past.

So, you know, there are a lot of positive incentives like that coming along where funders say yes, we realize that this takes time and we will pay for it. There are also very positive incentives in that Regulators have become much more helpful with this. So if you were trying to upload the result of a drug trial in Europe 10 years ago as an academic, you would have been completely on your own with a very complex system.

Today, you look at the European Medicines Agency's website and they've put up a manual, they've put up videos, they've put up a lot of training materials. So they're really trying to be helpful and to make life easy for people. And that's the way it should be. We all want researchers to be concentrating on actually doing research.

We don't want them to be sitting in front of a screen spending hours trying to figure out how a trial registry works or anything. We want these systems to be as simple as user friendly as possible and for everyone to use them routinely and for everyone to routinely get paid for using them as well for those few days.

It's only a tiny part of the total cost of a clinical trial of course. But it should be paid for and it should be recognized. And part of the work that we're doing when you said, can we create positive incentives? We create those incentives for institutions because I think we can't hold individuals responsible for these things.

It's ineffective. It's inefficient. So we hold institutions responsible for this. And when the university does a great job at This when they build a system internally, where they track every single clinical trial, where they remind their own researchers, we've seen that again and again in various European countries, that's when things really start to change.

So we put out these ratings and rankings of universities showing exactly which universities are doing well at this and which universities aren't. And if they're doing well at it, we very much positively highlight that. We highlight that as best practices and there are very few major universities in Europe that haven't started setting up systems like this.

And if you're looking at drug trials until Five years ago, pretty much all universities were not following the law in Europe. They didn't even know about the law. If you're looking at it today, the major universities in most countries, they're doing it. They've put these systems into place, they ensure that it happens, and it's been a huge benefit for patients and for science. And part of my job is Drawing public awareness to these great institutions saying look these people have done something fantastic here.

They've done something really beautiful here. You know, can we please have a round of applause for them so that this gets publicly recognized.

No, that's great. That's great, Till. And it sounds all positive that things are changing in the right direction. Thanks to people like you. Thanks to organizations like TranspariMED. I have one last question. Actually, two last questions. And the first one is actually, regarding what you mentioned that TranspariMED as an organization wants to raise awareness, but also build solutions,

Encouraging transparency. Can you tell me more about the solutions and also, kind of a sub-question to that you mentioned that it can take up to a couple of days to report your results, is that really that complicated? Can we make it more simplified? And is that something that you're also working on?

That's absolutely something we're working on I mean, we've already convinced the European Medicines Agency to make it easier to upload results. They've improved a lot, but I think there's still a long way to go. It shouldn't have to take That long, I think we can all agree on that. And that's an ongoing thing.

And the European Medicines Agency has started listening now to academics, and to academic institutions, and is in a dialogue with them and tries to make the process simpler. So that's absolutely something with the solutions. I'd say the easiest solution. Very easiest solution in the European Union is national medicines regulators to enforce the law.

I mean, you're regulators. That's what you're meant to do. You're meant to enforce the law. So if you have national medicines regulators in Europe enforcing the law, you've already got half of the problem solved. Then, as I said, public research funders, look at what the World Health Organization says, what you should be doing on the TranspariMED website.

You can find like an 11-point checklist where you can check, are we doing this? Are we doing this? Are you doing this? If you're doing all those 11 things, then you won't be wasting any money on invisible science at an institutional level. If you run a clinical trial as a university, as a hospital, as a pharma company, if that is happening under your roof, you have an ethical responsibility, you have a scientific responsibility, and in many cases you also have a legal responsibility to make sure that the results are made public.

So are you keeping track of that research? Are you ensuring that the results are made public? Yes or no? If the answer is, uh, no, we're not doing that right now, you can go on to the TranspariMED website and you can find a manual for universities and hospitals on how to set up these systems. Because so many institutions have done this successfully.

You don't have to start from zero. You can simply copy what other people have done. And that's a lot of what we're doing is we're just bringing people together to have these conversations about how can we make it easier? How can we make it faster? And also just bringing people into a room who've already done it with people who are still working on systems like that.

And just enabling them to exchange experiences. So when you look at the TranspariMED website, it's like looking at noise. You're seeing 10 percent of the work. 90 percent of the work just happens below the surface and that's just introducing people to each other, helping them, and just trying to get a dialogue and getting things forward.

But things are massively moving in the right direction. It's a one-way street and it's a ratchet effect. If you're a hospital and you put up a system tracking which clinical trials you're running, That system will still be there in 50 years because it's such a commonsensical thing to do that you're never going to consider, you'll look back in 50 years time and you'll go, Oh, I can't believe we didn't use to have a system like that. Yeah.

No, you're absolutely right, Till. You're absolutely right. Yeah. And, you kind of like summarize it by saying we shouldn't start from zero. That's actually with clinical trials makes no sense because we have clinical trials for so many, many years.

We've learned so much. So. Clinical research, we speak, it's about collaboration. Transparency is part of this collaboration. I really hope that we'll see more and more collaboration, no matter public research, commercial research, whatever research. One last question, Till.

What makes or breaks clinical trials from your perspective?

Well, if I had to put it down to one word, it would be usefulness. Is the trial useful? And, from my perspective, what I focus on is, of course, are the results made public? Because if the results are not made public, then the whole trial is useless. It doesn't benefit anyone, but then when you're thinking about usefulness, then, you also got to include has this, is this actually a scientific question that is still open?

So, for example, if you're running a clinical trial of hydroxychloroquine for COVID treatment today. That's not useful because we already know the answer. So it's a combination between, the research question and then the research design is the trial actually designed in a way that it can answer that medically or scientifically important question and then at the end it's.

Were the results fully made public? So, yeah, I'd say it's very simply usefulness. If you're asking the wrong questions, if you're running the trial badly, or if you're not making the results public, it's not a useful trial, and you shouldn't be asking patients to come in 30 times and give their blood and, consent to all these invasive measures.

Um, people have got better things to do with their time. People's bodies are precious. Um, if you're not running a useful trial, then please don't run the trial in the first place and maybe think about changing careers.

Wow. Till, that's absolutely inspirational conversation. Uh, at least you inspired me, but I'm pretty sure that everyone listening to this podcast episode will be inspired as well. Thank you so much for giving me some light into the transparency world of clinical trials. I definitely learned a lot of things from this conversation.

Thank you for sharing your time and your know-how in the space and, yeah, keep doing what you're doing Till, because that's absolutely valuable. Thank you.

It's not just me. It's dozens of groups worldwide that are working on this now. And, um, yeah, we'll keep up the good fight. No worries there.

Thank you all and keep up the fighting. Exactly. Thank you. Bye bye.

Cheers. Bye.