Our industry is often resistant to change. Even though the world doesn’t look the same today as it did even five years ago, our industry still does things the way they were done 30 years ago. It’s time to look past what we've always done and adjust. If we don’t, we’ll be left behind.
I believe that the key to change in the CRO industry is investing in and leveraging data and technology. I’ve seen this change happen firsthand.
I landed a job in the CRO industry in 2001. I worked in the periapproval group of a large CRO. “Periapproval” means around the time of approval—whether it's pre-approval (you've done all your pivotal trials or phase III studies, and you've already submitted for approval) or you're looking for a label change or new indication.
When I started in the industry, the periapproval space experienced a shift in focus related to safety data in a real world setting. There was a lot of press surrounding new, unexpected drug safety events that occurred after drug approvals, and regulators were pressing sponsors to do more post-approval research on approved drugs.
Clinical trials are well-controlled, with a specific set of entry criteria and close patient monitoring. When new medications are available to the general population, where patients look and act differently, you start to see things you didn’t expect or see in your research studies. This led the FDA to drive more initiatives towards Phase IV or “real world” research studies like registries. I jumped into the industry when these trends started to gain steam.
Eventually, while working at this CRO, the amount of business we received was less and less periapproval. It started to shift heavier in the clinical trial/registrational space. I was assigned to more and more phase II/III research studies. It wasn't a choice.
After doing that for a few years, I felt that my day-to-day work started to look the same. I worked on heart failure studies. I worked on diabetes studies. I worked on asthma studies. Every single study, although they had different nuances related to that therapeutic area, all struggled with the same challenges.
How do you get sites activated quickly? How do you get patients recruited quickly? How do you get data monitored and cleaned quickly? The scientific question is always the same for them. They’re always trying to find out what medication is better than the current medication. In order to do that, they design a study that looks similar.
It was a constant dance between timelines and study design. You tend to implement the same mitigation strategy when you have studies with recruitment challenges. You advertise and you create flyers, brochures and referral letters, but recruitment is left to the site’s capabilities and their willingness to recruit.
It felt like Groundhog Day for me! It felt like I was always doing the same thing and my day-to-day work never changed.
I left that first CRO to work within PRA’s Real World Solutions group. When I interviewed here, I finally felt like people were speaking my language. PRA doesn’t do those “one size fits all, just throw in a different therapeutic area” trials. Here, we figure out ways to troubleshoot what scientific questions we're trying to answer. We help to design studies that get that question answered in a lower cost, high efficiency, low burden manner. That was very appealing to me—the opportunity to think outside of the two or three problems I was constantly solving on every study.
Sponsors are notorious for wanting all possible research questions answered—an “everything but the kitchen sink” mentality. Studies are designed with loads of objectives and endpoints. What actually ends up happening is that the objectives are so broad and extensive that it’s hard to answer anything. Our Scientific Affairs team is great at helping sponsors design protocols that answer the most important research questions in the most effective way.
I think a great example of troubleshooting a scientific question is PRA’s involvement in a trial called CHIEF. It’s the first completely decentralized, interventional, indication-seeking clinical heart failure study in the US. That trial came about as a conversation between friends who wanted to broaden and change clinical research and do things that have never been done before. We’ve been told by the FDA that the industry is ready for this to happen, but nobody's had the nerve to do it—until now.
Our sponsor provided much of the background and study design. They helped us get into the therapeutic area. This positioned us within the therapeutic space to find Integrated Delivery Networks across the US to be good “site” candidates for the study, as well as own the medication we're testing.
To figure out how to conduct CHIEF, our teams came together and brainstormed ways to implement a fully decentralized, randomized, placebo-controlled, double-blind study for a label change that had never been done before in the US.
On top of that, we knew some recommendations were certainly being pushed by the FDA about using secondary data—such as medical claims and doing more virtualized research, but with no full blueprint.
We worked hand in hand with the sponsor to develop not only the protocol, but the technology as well. We had to make it user-friendly for a patient since the trial would be done from the comfort of their home. So much planning was involved—more than any research study I can remember. We planned for CHIEF for about six months.
CHIEF’s patient population—people suffering from heart failure—is challenging to begin with when you start to talk about technology. We didn't really know what to expect. What we found was that people actually are much more tech-savvy than we expected. The saying also holds true: if you build it, they will come. We built this huge platform to recruit people virtually. Currently, we have about 1,400 people who hit our platform, and that's only within three months.
We've faced other challenges—for instance, we find the patients, but they're not always the right patients. Again, this is a registrational study, so we have to meet certain eligibility criteria. When you start looking into a patient’s medical chart, not all these patients fit that criteria. That happens in research, but it’s happening more heavily on CHIEF than we expected due to the nature of how patients are recruited.
Still, we're recruiting at a much higher rate than you would in a typical heart failure study, and we’re using large health networks which gives us a broader patient pool. We are recruiting 11 patients per network per month. Standard heart failure studies recruit somewhere around 0.3 patients per site per month. So, it's a success when you look at it from that perspective. Still, we thought we’d be done by now. We're not.
For so many years, we’ve focused all of our time trying to bring patients to the research. Virtual and decentralized trials flip that mindset—the research is brought to the patients.
Patient-centric research gives patients the opportunity to “opt-in” and be part of their clinical decision-making on the front end, instead of us always chasing them down. We're able cast a wider net, which definitely expands our user profile. On top of that, CHIEF’s design allows us to gain a robust clinical perspective of the patient. By using medical insurance claims data (prescription pharmacy claims, and hospital claims) to follow patients throughout the course of their participation, we can follow patients longitudinally throughout their participation in the study instead of just relying on sites to data enter everything directly from source.
On CHIEF, all of the data is coming directly from source (the patient, a wearable, or directly from their insurance claims). This gives us a better view of the patient’s healthcare over time.
We are also starting to look at the dynamic of the people who we treat and what their general care patterns look like. If we don't create research around their care patterns, we're not going to have anyone enrolling in studies. It’s also important to look at the generational changes that are happening with our patients, ensuring that we're designing research that aligns with their values and healthcare options.
Previously, we’d recruit patients while they are sitting in a doctor's office, or run ads on the radio or TV. Now, we're doing social listening through social media platforms. We can actually digitally identify where patients or caregivers are looking for research opportunities in a specific location for specific disease states. We are partnering with advocacy groups. PRA is trying to keep up with how people’s daily lives are changing. We’re using all possible resources that currently exist to pull it into the research agenda.
Trials like CHIEF are good examples for how we might handle disaster situations, such as the current pandemic, in the future.
We launched CHIEF days before the pandemic hit and things started to shut down. We did all this work thinking that we were starting the first virtual research study, and then about two weeks later, everyone wanted to do virtual research in the wake of the virus.
By spending months preparing and troubleshooting on CHIEF, we've seen what works and what doesn't. It’s given us insight and experience that other CROs who haven’t dipped into virtual research won’t yet have. They're just getting on board with COVID-19.
If the future of research moves to be more virtual, PRA is best positioned for this. I do think that COVID-19 is going to accelerate changes in drug development as a whole. Sponsors have been forced to find solutions on how to do more research virtually or in some sort of hybrid manner, whether using telemedicine, eConsent, Home Health or direct-to-patient IP shipments. We can finally see a shift in the industry starting to happen, and I hope it lasts.
I mentioned that it’s challenging to change mindsets in this industry. My previous company was not a risk taker at all. We were always three versions behind any tool that anyone else was using, or we weren’t using them at all.
It was thrilling for me to see that PRA leadership invest in technology and tools that allowed us to shape the CHIEF trial, stay on the cutting edge of this industry, and make study management easier and more effective.
We've invested in companies that will make us more relevant, such as the acquisition of Symphony Health, our new Mobile Health Platform, and Care Innovations. Every investment is a risk because you have no idea how things might turn out. It’s challenging to integrate new companies into your day-to-day operations. It takes time to build that out before you see the return on your investment.
I think it's amazing that our leadership took risks, estimated where research was going, and got ahead of the curve. We're able to build out our virtual/decentralized clinical research options for sponsors in ways that offer a lot of opportunities for the future of research.
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