Dr. Stephen Renard on Academia-Industry Partnerships

Automatically transcribed and lightly edited
Michael Lyon: This is "Heartbeat," conversations about medical science, research, and the discoveries that touch our lives, in collaboration with the University of Nebraska Medical Center.I'm Michael Lyon. My guest today is Dr. Stephen Renard, professor, UNMC Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Nebraska Medical Center. Today, we'll be talking about why partnerships between academia and industry are so important in medical science.From August twenty fifteen through November twenty nineteen, you worked at AstraZeneca in Cambridge in the UK, as one of their chief clinician scientists, which more than qualifies you to talk about our topic today.And I'll start by asking you why are partnerships between academia and industry so important in medical science?
Stephen Renard: There's several things that medical science does. It's a subset of science as a whole, but medical science, if, to break it down, the two important things that medical science does is first to understand how health and [00:01:00] disease works, and second, to try to make new treatments for illnesses so that people can be better than they would have been.Especially the second part of that, that is to make new treatments, is a very complicated process. and what's required is to bring some kind of concept that something could make you better, to full understanding that it actually does do what you think it does, and it's actually safe for you to take it, within the realm of, limits of understanding.That's a hugely, complex, expensive, task that really requires lots of different kinds of expertise, and almost always is done through a collaboration between academia and industry.
Michael Lyon: To effectively, advance the medical science. In other words, there are dual roles that are vital to each other.
Stephen Renard: Yeah.
Michael Lyon: So, when people hear about a new treatment, they often don't realize everything that goes into it [00:02:00] or how long the journey has been. What does that sort of path briefly from scientific discovery to patient care typically look like?
Stephen Renard: Okay. I think your comments about the path are correct. It takes a very long time, to go from the discovery to the treatment. a very recent one, for example, for sickle cell disease , okay, as diseases go, it's not complicated. It's just one change in DNA that causes hemoglobin, to be abnormal in the people that have that DNA. but it causes a terrible disease.The disease was discovered a long time ago, but the fact that the DNA responsible for it was discovered, decades and decades ago, and it's only just now that there's a treatment that actually can correct that.It took lots and lots of basic discovery, which primarily is done in academia, and then for those basic discoveries to be applied into clinically meaningful, meaning things that are safe, and effective, and then to [00:03:00] prove that's the case, it took a very long time.
Michael Lyon: So the difference between discovery and delivery, in other words.
Stephen Renard: it's more than just discovery and delivery. So, there's, and sickle cell is not a bad example. The discovery of the gene for sickle cell disease was only part of it. It then required, an, a large number of other discoveries. for example, how do you actually change the gene? And how can you actually get the gene changed in a living person, and do that with some confidence that it can be safely done?Those all required a whole series of additional, important discoveries, and I'll say important Nobel Prizes in that particular example. most of that was done in academia. there are Nobel Prizes that have been awarded to industry scientists, so it's not an all or none kind of a thing. But then there's the implementation phase.How do you actually take a discovery and make it into a medicine? That's largely done in industry, but not exclusively. So, there's lots and lots of overlaps, [00:04:00] as you might expect for something that's really complicated like that.
Michael Lyon: And the clinical trials, of course, are often described as the bridge between the lab and the clinic.Michael Lyon: Why are they so important?
Stephen Renard: You might have an idea that something might work. Okay? you've made some discovery, and you think that you can make a medicine based on that discovery. you might be able to make a molecule that you think might be able to become a drug if it really worked. You could test it in an animal model, which means, of course, you have to discover how to make the model in an animal.And you could do that and provide some evidence that it seemed to fix what the animal got that seemed to be like what the person got. And that gives you some suggestion that maybe it would work in people. But lots of things that work in animal models do not work in people with the disease of interest, sadly.So at some point, you actually have to test it in people. There's real ethical questions about that, okay? Because you're giving people some molecule, it might be, it might be very [00:05:00] effective, but it also might have side effects. the side effects may be such that you can't use that medicine at all.It may be that the side effects are manageable if the disease is bad enough and the medicine actually cures a bad disease. So, the clinical trials, which is the bridge between those discoveries and taking it into people, is really all about balancing the risks and the benefits, which obviously is now gonna require very careful clinical observation of the people that are participating in the experiment where the medicine is given.
Stephen Renard: And they're a promise. There's been lots of examples of where people have been enthusiastic about things and have done medical research where the participants in that research have suffered as a consequence. And so it's extremely important that all of this be done under very careful ethical supervision to protect the rights and optimize the safety, for the people that are participating in [00:06:00] medical research.So it's not a simple process.
Michael Lyon: So, without getting too deep into those details, those regulatory details, what are some of the ethical and oversight considerations that guide these partnerships?
Stephen Renard: Okay. Well-
Michael Lyon: I'm talking about patient safety, informed consent, things you've touched on, and, compliance with regulations that maintain scientific integrity, for example.
Stephen Renard: all of this has evolved over the last hundred years. And to be fair, th-this has evolved sometimes because things weren't going as people thought they should have done. We don't need to recant the various kinds of medical research that is now not regarded as ethical, but it's very important that people not forget about those either.
Stephen Renard: and so we really have a system that, that really has three main principles. There's documents on this. All medical researchers doing human studies, have to be familiar with these, and our regulatory process has to do it. But the three basic principles are that people have to be volunteers, and they [00:07:00] have to be able to decide that they really wanna be engaged in the experiment, and they have to understand what's, what the experiment's all about.What are the risks? What are the potential benefits to them and to society? And they should be able to make, a, an informed decision that they're willing to do this. and there's lots of reasons why people might want to do that, and there's lots of reasons why they might not want to, and if they don't want to, then they shouldn't.Furthermore, they should be able to change their mind and if you learn something new about the drug as you're studying it, you can't withhold that information. That would be seriously unethical 'cause that could change the way somebody would think about the experiment, and they may decide that it's not for them anymore.And so what's called autonomy, people need to be able to make those decisions, and that's what informed consent is all about. But there's more than just that. you have to actively try to minimize the risks to people, so all right, everything has risks. If people say that this is risk-free, it can't possibly be true.There can be [00:08:00] minimal risks, but the risks need to be explained, and you need to minimize those risks.And so for example, if I wanna, draw blood from you, there's minimal risk when drawing blood. But there is a possible risk that you could pass out, so I really should draw that blood from you under circumstances where if that happened, we minimize the risk. You shouldn't be standing up or sitting on a bar stool with wheels and no handles.And you can imagine ways in which you would draw that, like what happened at the hospital, where Your safety is being optimized, and that principle needs to be extended to everything that's done in a research study. And then the third principle is that it has to be fair.You can't do the research in people because it's convenient for somebody else. for example, you can't study, people in another country that doesn't have access to medicine to develop a medicine that you expect to use in your country. It's gonna be too [00:09:00] expensive, and the people that are doing, putting themselves at risk to do the experiments wouldn't be eligible to get that medicine.that would be, regarded as unethical by current principles, and I could think of lots of other examples where there could be an unfair distribution of the benefits of the experiments where the people participating in them are un-unable to derive. So all of those ethical principles are inherent in, conducting studies.And then a very important principle is the investigator should not be the person responsible for deciding whether the study is being conducted ethically. That is, it's impossible to make that decision about your own research. You're enthusiastic. You believe that you're doing the right thing, and you're giving informed consent and you're optimizing safety and whatever.If you didn't, then you wouldn't have proposed what you've got. But somebody who's not engaged in the research and isn't connected to the research in any way that can give a dispassionate [00:10:00] view, of whether that's really the case from their perspective needs to be done. And most IRBs that are responsible for making these decisions believe that their composition, the composition of the members of the IRB, has to have lots of different perspectives of people. Some people should be medically expert and be experts in the kinds of things that you're doing.But there needs to be some people that aren't there because of their any medical expertise, but because they've got a social perspective or a cultural perspective. and so, I think we have a certainly much more mature now than existed fifty or sixty years ago, in the United States, to conduct research ethically.It's always gonna be a work in progress. But of course, all of these safeguards, and make no mistake, they are absolutely essential, add complexity to the medical research environment. complexity means increased costs, and increased costs means that, for things that are big enough, you get into industrial kinds of activities, [00:11:00] and so that leads to reasons why industry and academia need to collaborate.
Michael Lyon: Collaboration, of course, sounds ideal, but there can be tensions. One of the issues that's often discussed is balancing scientific openness with intellectual property protection. How do organizations navigate that?
Stephen Renard: I can comment about that since I've been, I wouldn't call it a participant in it. I certainly don't, don't, promise to be any kind of expert in that.but there's some interesting paradoxes. So, for example, you might say that if you're an academic investigator and you're interested in understanding disease and you want to discover a new cure, you're not interested in making any money, so therefore you don't want to patent anything.You just want to make your discoveries available for everybody. as soon as you can't patent it, okay, nobody can make any money from it, then it's not attractive to an industry. By definition, industry, at least in our [00:12:00] jargon, industry is companies that are for-profit, and they're set up and they have shareholders, and the shareholders expect to get return on their investment.they're not non-profits. We can talk about non-profits and research 'cause there is a role for that, and it's really important and it fits in between the spaces we're talking about now. But a for-profit company won't make a $2 billion investment in a potential therapy if in the end of the day, they prove it works, everybody can sell it, not just them.Because there's no way for them to then recoup their investment. There's lots of details there obviously, but the interesting paradox is that if you don't protect the intellectual property of a new discovery, you may make it impossible for that discovery to lead to a new cure.The universities I think are eager to, develop intellectual property. That's seen as a revenue stream as well as to try to bring the discoveries to the clinic. The NIH, [00:13:00] for example, that funds much or if not most of new development of intellectual property at universities takes a very interesting attitude.They want the universities to patent it. The NIH doesn't want to patent anything, and so they're perfectly happy to assign the intellectual property. And then for some grants, that becomes a grant review criterion is the intellectual property going to be protected so that the discoveries, if any, are made, can be taken forward, at least in the current way we do business, to developing therapies that patients can actually take after development is complete, assuming everything works.
Michael Lyon: another concern is maintaining public trust. How can institutions manage conflicts of interest while still benefiting from industry partnerships? I'm thinking about disclosure of financial relationships, independent oversight, peer review, et cetera.
Stephen Renard: this is an interesting thing in terms of what [00:14:00] constitutes a conflict of interest.one of my, former associates, he's passed away now, is a patient, head of a patient group. If we get an opportunity to talk about the role of nonprofits in medical research, we may get to that. But, used to quote his father, who I'm sure was quoting somebody else, about conflicts of interest, was that if you're not conflicted, then you're not interested. And everybody has conflicts of interest. And so, one of my pet peeves is people who will give some lecture, and they'll say, "And I have no conflicts of interest." that's-- can't possibly be true. people have conflicts, and there's always conflicts. if you're an academic researcher and you don't own any shares and you don't have any, patents, and you've got no industry disclosures to make. That's fair. On the other hand, if you make your living taking care of people with that disease, then you're talking about the disease and why you're such a good doctor, that's a conflict of interest, right? you may not, be an advertisement for people to come see you in your mind, but it is, and [00:15:00] it represents a conflict of interest.So conflicts of interest are, again, things that nobody should ever decide for themselves. you can't decide your own conflicts. Somebody else should be able to decide for you. and there will be conflicts. You can't be free of them. and so complete disclosure is required. They should over-disclose, in my mind, rather than under-disclose. And then some other agency needs to decide if those disclosures represent conflicts, and then if the conflicts can be managed.And sometimes there's simple management programs. Sometimes there's more involved management of conflicts. And sometimes they're unmanageable. So, for example, if you are a discovery of some new medicine that treats some new disease, and you get a grant to study that, and you're gonna do clinical studies to study this, and it's a bad disease, you have a chance to cure it, you're all [00:16:00] excited about it, and you've set up a company that's gotten money from investors to develop the drug.All right? Now, you have a conflict of interest here. That's pretty obvious. So, what role can you have in this study? I think most IRBs would say you really cannot be the person who gives informed consent somebody else has to do that. There's no way to manage your informed consent. could you be involved in evaluating the data?Probably not if you know who's been treated with what, right? You're an unblinded observer, making decisions about how to go forward ... You've got a clear financial and personal interest in how the study goes. So that would be, another conflict that couldn't be managed. But you could manage the study by saying that you will never see the data before it's been evaluated by others, okay?Or you will [00:17:00] never be a person involved in making clinical decisions or giving informed consent for the people in the study. the individuals responsible for that need to be able to put the patient's safety as the highest priority without an unmanageable conflict for financial reasons. There's been examples of that happening, as you might imagine.And this is why people shouldn't decide it for themselves. You shouldn't say, I believe I can fairly divorce those that..." Maybe you can, but somebody else should make that decision.
Michael Lyon: So, we're talking about a balanced, transparent ecosystem with lots of guide rails and independent observers.Another part of that, of course, is that funding priorities often can shape what research gets done. So along The lines of this balanced ecosystem, how are commercial interests balanced with broader public health needs?
Stephen Renard: this is an area where I think that there's, [00:18:00] real tensions, okay? having done this from many different perspectives.any drugs that we have are what's called me-to’s, so somebody develops a new drug for an unmet medical need, and it-- the drug is a blockbuster, and they're making gobs and gobs of money. but the drug has to be taken three times a day, and it tastes bad and, whatever. if you think you could make a better drug that you only have to take it once a day and it won't taste bad, you can say, there's a multi-billion-dollar market.We can get a chunk of that market. We already know how to develop the drug. Somebody's already shown us that if they did this and that and the other, and they got it approved by the FDA. So, if we do this and that and the other with our drug, the FDA should approve it." If you're now working for a company that's owned by shareholders, and your responsibility, if you're the president of the company or the CEO or the chairman of the board, how do you prioritize that kind of research where [00:19:00] it's pretty clear you'd be able to live up to your fiduciary responsibilities, which means, making money for the investors, as opposed to there's a disease that has no cure and no effective treatment, and somebody's now got a new idea that's very plausible about how you might be able to fix it, except that nobody's ever done it before, and you're not even really sure what you can measure to actually show this in any short period of time if it's a slowly progressive disease.And so, you have an uncertain pathway to getting your drug to market, and you don't know what the FDA is likely to require. And then when you did get it to market, it's very unclear how you'd be able to sell it. there's no market. You can guess, and the people, companies hire marketing people to try to sort that out, and they do a surprisingly good job.
You now have a clear pathway to develop a drug that's a marginal [00:20:00] improvement over what you've already got, but it's better and a pretty sure bet that it would give you substantial return on your investment or something that could do something much more important, but it's a huge gamble, and you don't even really know how expensive it's likely to be, even if it is gonna work.And pretty much most of the time, you're gonna probably bet on one rather than the other if your responsibility is to the shareholders. And so that tension comes up all the time in industry.
Michael Lyon: When we look ahead, we're seeing more and more collaborative research, networks, shared data platforms, public-private partnerships, and interdisciplinary teams.Do these sorts of advances, especially in areas like artificial intelligence, precision medicine, and other things.Do those give you optimism for where these kind of partnerships and collaborations are going?
Stephen Renard: Oh, sure. [00:21:00] f-first of all, nobody is expert enough to do everything required to bring a discovery to become a treatment.You can look at it in terms of the money, okay? So if you wonder, "Why does it cost $100 million to make a movie?" And the answer is, when you look at the credits at the end and how many people were involved in making the movie, you get an impression of, okay, if all of those people got a salary, even if they only worked part-time on the movie, and not everybody is listed in the credits, that's why it's so expensive.A movie costs $100 million. A new medicine costs two billion, so that's 20 movies, and It's almost all salaries. Even the manufacturing of the drug is the salaries of the chemists that are doing the manufacturing. So, this is mostly people. Some of the people have shared expertise, but it's people with many different kinds of expertise. So, it has to be done by teams, very big teams. And the more effectively teams can be organized to do things, the more efficient [00:22:00] the whole process is gonna become. So yeah, I think, over my career, which goes back, happily a fairly long time, I've been able to see the evolution now of teams being to approach clinical problems, that were really unsolvable before because the size and skill sets combined into the teams didn't exist.And it's a tension between scope and autonomy. To participate in these teams, you have to be a team player, on the other hand, you can do things that couldn't be done by individuals working alone.
Michael Lyon: My guest today has been Dr. Stephen Renard, professor, UNMC Division of Pulmonary Critical Care and Sleep Medicine at the University of Nebraska Medical Center.We've been talking about why partnerships between academia and industry are so important in medical science. I'm Michael Lyon, and this is Heartbeat.