Research and devolvement (R&D) scientists in life sciences are constantly on the lookout for innovations that will improve the likelihood of a successful end result. Over the past few decades, advancements in computing and technology have dramatically transformed the capabilities and capacity of life science R&D, a shift that has been fundamental in the emergence of concepts such as personalised medicine.
Patient-centricity is now a central pillar of innovation for many leading figures in life science. As such, scientists are beginning to adopt new processes in the lab, which reflect the changing needs of patients and health care professionals.
With 25 years of experience working in the pharmaceutical industry, Astellas chief medical officer, Bernhardt Zeiher, has been in a prime position to witness the transformation of R&D. As the industry lays the groundwork for a new era of health care, Zeiher explains how a global pandemic became a catalyst for change, putting patients at the heart of life science research.
I think it really comes down to a tremendously greater understanding of the pathophysiology of disease. For example, in oncology, understanding driver mutations for different malignancies, or the role of immune surveillance and cancers evading that immune surveillance, because that’s really led to then identifying targets.
The other driving force is probably technological advances. Cell and gene therapy, some of those things were almost like science fiction when I started my career. Now it’s coming to fruition and we are really seeing the advances there. I think those have been really the biggest drivers of change in R&D.
COVID was a tremendous catalyst for change. Just figuring out how you continue to run trials because patients are told they’re not supposed to go to the hospital. What do you do with clinical trials if it’s not for a COVID indication?
It changed a lot of our thinking. Now it opens up to saying, “Do we have to run our trials the same way? Can’t we run them differently? Can’t we make them more patient-friendly? Can’t we give broader access to clinical trials because of what we’ve learned?” Some of these things were already happening, but it has happened much more quickly because of COVID.
One of the things we’ve tried to do with clinical trials is to make them more patient-friendly and engage them throughout the life cycle. Sometimes when you get into rare diseases, the patients or the caregivers know much more about it than anyone else.
Too often – and as a physician, I can say this – we’ve taken a rather paternalistic view that this is what people want. But maybe they value different things. Understanding patient and caregiver needs is important because, even though it might not be an endpoint that the regulators want, it could be an endpoint we still want to measure and make sure we’re demonstrating that value for patients.
Enrolment is always a challenge in trials. One of the most costly things that can happen is if you have to change your enrolment criteria – there’s a lot of evidence that amendments are very expensive and delay the timelines. Getting patient input earlier can help with a better design study that will aid recruitment and retention.
Getting patient input on what they’re willing to do in a clinical trial also matters because the other thing that can happen in trials is that patients enrol and then say, “Well, I didn’t realise I was going to have to come back to the office so much or have this done”, and then they drop out.
There are more trials than there are patients in some cases, and we need to make them more accessible to individuals so that they enrol and participate and hopefully, we can bring therapies to patients faster.
This has been a problem for quite a long time. It’s very important that we do address diversity in clinical trials because different populations could have different pharmacokinetics, safety, or efficacy. That way, if there is any difference, we’re aware of it.
There has often been some mistrust of institutions among some underserved populations. Our approach has been to go to sites where you’re going to be able to recruit a diverse population. We also try to get institutions to commit to offering this more broadly.
One thing is the site selection; the other is that we can make our trials more accessible. Some things, like allowing virtual visits or transportation back and forth, at least make it more feasible for people. If they have to pay for a taxi ride every time and they don’t have the means to do that, they’re not going to want to participate in the trial.
We also support the Pharmaceutical Research and Manufacturers of America’s (PhRMA) industry-wide principles on enhancing diversity in clinical trial participation, and trying to educate about clinical trials. In some of our trials, we also try to partner with community groups. There isn’t an easy solution, but I think that’s why we’re trying to at least take a multi-pronged approach.
What you really want to do is retain all the good things that have come out of the pandemic, like the ability to run studies more remotely and make them more patient-friendly. A lot of it is just changing your mindset to think about what’s going to be easier on patients upfront. Sometimes it takes more time because you may have to engage with a patient group or get more input from other people.
That’s where I think the pandemic served as such an accelerator because the usual way we do it would be, we’d say, “Oh, we’re really interested in running a decentralised trial, let’s run a pilot”.
Well, the timeline to do that is a couple of years because an individual trial takes a year – often, it’s longer than that. There’s planning upfront, and then there’s rollout more broadly. There was no opportunity to do that with the pandemic, and all of a sudden, we had no choice. You couldn’t do the pilot. You had to do everything on every trial now. I think there’s a much greater willingness to try new things because we did it in a crisis situation. So, why can’t we do it now?
When you can think about digital in helping drug discovery using machine learning and artificial intelligence, as well as the ability to handle big data even in our clinical trials, you can identify trends that might tell you where you need to go from a quality perspective, or where we need to go do a site audit.
In the past, I think it was a little more “We need to audit six sites, and we do it midway through the trial”. Now, it’s like, “Well, no, let’s see where there might be something that looks different”. And then we’ll go audit there.
I think there’s going to be more and more use of real-world data. We use it to help guide us, even on designing protocols, where you can look at what co-medications they’re on, where patients could be located, and I think that’s going to continue.
Whether it be rare disease or a well-characterised subset of a more common disease where you look at either genetic or biomarker-driven phenotype that you can really target, real-world data gives you potentially much greater opportunity for efficacy, and it’s allowing for some safety, so you can really shift that benefit to risk balance.
I think it’s tremendous that we can have a broad impact working on a product that then gets used by people and can change their lives.
Bringing patients closer to our trials can be incredibly motivating for the industry and also ensure that we’re working on the right things.
Unfortunately, the industry sometimes gets a bad rap. But, when you hear the real stories and get a letter back from someone who said, “We’re so grateful that you were able to provide the drug for this individual”.
When you read those, you know why you do what you do.
So, I’d say bringing patients closer can only benefit us in not only driving that sense of urgency and passion for what we do, but also ensure that we’re working on the right thing and that we bring those medicines to patients.
Dr. Bernhardt “Bernie” Zeiher serves as chief medical officer and has responsibility for overseeing all functions of Astellas’ Medical and Development organisation, which includes development, medical affairs, regulatory affairs, pharmacovigilance, quality assurance, and planning and administration.
Prior to his current role, Bernie served as president of development where he was responsible for all stages of drug development at Astellas, helping to build world-class oncology and medical specialties functions for addressing serious unmet patient needs across multiple disease areas.
Eloise McLennan is the editor for pharmaphorum’s Deep Dive magazine. She has been a journalist and editor in the healthcare field for more than five years and has worked at several leading publications in the UK.