Clinical research strategies for 2020 and beyond

If you’ve been following the Crohn’s & Colitis Foundation, you know they've been busy making innovative changes to their research approach. They have been working to improve the way IBD clinical care is delivered through IBD Qorus, which is designed to bring patients and providers from across the United States together to identify and share best clinical practices. Their investment in SPARC IBD (which will collect and analyze data from over 7,000 adult IBD patients for years) will generate an in-depth bank of patient data that can be used to answer many questions. 

The Foundation has also pioneered IBD research in areas that are usually not funded by pharma or biotech, such as their investments in microbiome and nutrition studies. Leveraging funding from the Patient-Centered Outcomes Research Institute (PCORI), they launched DINE-CD, the first randomized national clinical trial to test two dietary interventions in Crohn’s disease. The Foundation is committed to exploring new research directions and ensuring that patients are actively included in the research process.

With so many changes happening across the medical and research landscape, the Foundation felt it was critical to bring together a broad range of stakeholders to ask the question: in today’s research environment, how can we work with our partners to get faster and clinically important results to patients in 2020 and beyond? 

With that question driving an ambitious agenda, last year the Foundation convened a daylong conference on clinical research strategies with over 80 attendees, including participants from leading research and academic institutions and non-profits, industry partners, and patient advocates. During the event, they looked at the following questions:

  • How can we ensure that patient priorities are front and center in clinical research?
  • How can we improve clinical research, and make results more usable in the real world?
  • What are the high impact research questions we should focus on going forward? 

Below you’ll find a recap of what I learned from the conference and its implications for the IBD community in 2020 and beyond.

The patient perspective on clinical research participation

Tina Aswani Omprakash, Crohn’s patient, public heath advocate, and creator of the blog Own Your Crohn’s, kicked off the IBD Clinical Research Strategy Meeting with an impassioned call to action-- based on her first-hand experience. Tina, who’s lived with Crohn’s for over 14 years and endured multiple surgeries, gave attendees a brief but powerful account of her journey, ending with her participation in a clinical trial: 

“I used to work on Wall Street in the banking industry, but this disease derailed my entire life. And then things got much worse, with an infected pelvic fistula (abnormal connection between the intestine and another part of the body). I was told this might paralyze me. I went to the Mayo Clinic, and my doctor worked like crazy to find a clinical trial that might fit my situation. Somehow, he got me into a trial. He took the time for many discussions with me so I could really make the decision to participate. And thanks to the clinical trial, I went into remission for the first time in 10 years. I’m now in year three of remission.”

Tina’s story speaks volumes about the potential of clinical research to improve lives. It also raises important issues about the need for improving patient access to, and education about, clinical research and clinical trials.

Patient and provider concerns about clinical research

Tina’s talk reminded me that, even though randomized clinical trials have been viewed as the gold standard for medical research since the 1960s, both physicians and patients have been raising valid concerns about them for decades.

In fact, it reminded me of a visit I made with my grandmother to our family doctor in 1975. My grandmother (who had frequent chest pains from angina, a type of heart disease) had read about a new cardiac drug and asked our family doctor if it might help her. He said, “I wish I knew, Yetta.  But the clinical trial for the drug excluded anyone who also had high blood pressure (like you), or anxiety (like you), or who was taking any other heart medications (like you). And most of the patients were younger than you. So, it’s hard to say.” My grandmother thought for a moment and asked, “How many angina patients do you have like the ones tested in the study?” “None”, he said. 

It sounds almost like a joke, doesn’t it? But it’s a real story, and I heard almost the same issue, when a gastroenterologist told attendees at the Foundation's 2019 conference:

“Patients in IBD randomized clinical trials don’t look like most of the IBD patients we treat…the...trial included only patients who had never tried immunosuppressive agents, and excluded pediatric patients and many patients with disease complications. That doesn’t represent most of our patients. And that happens a lot.”

Another attendee reminded the audience that a 2012 study found that almost 70% of IBD patients weren’t eligible for IBD studies! This research model is narrowly designed on purpose; it makes it easier to see exactly how a drug works in patients with just one disease or certain symptoms. But that leaves out a whole lot of patients.

A related problem: physicians in clinical practice generally don’t talk to their patients about clinical trials. As one physician said:

“Most of us—and I do this too—live and practice in an off-label culture. Instead of putting someone into a clinical trial, we reach for an off-label drug [a drug that hasn’t been approved for the condition for which it’s being used]. We need to realize that we’re putting people on drugs that aren’t well tested in terms of their IBD profile. And then, if we do try to test that drug in that population, that patient won’t be eligible for the clinical trial because they’ve already been on it. How do we put the horse back into the barn? With new patients who have not been on any drug, we should really try to get them into a clinical trial so we can all learn what will work best for patients with different disease patterns.”

New and innovative research models

The good news is that the research world has become more responsive to these problems. New and innovative research are designed to work with real world practices and provide information that’s relevant to a wider range of patients. Just to give you a brief overview:

  • Pragmatic clinical research is research conducted in real-world practices (versus only conducting trials in research settings). By setting the research in real-world practices, patients can continue to get treated by their regular healthcare provider instead of a researcher. These trials are designed to provide real-world results without placing a lot of extra burdens (like extra visits or lots of tests) on patients or healthcare providers. 
  • Platform trials are an innovative method that can be used to test several drugs at the same time. Researchers use a master protocol, which is a detailed plan that might describe, for example, which drugs will be used first, and what criteria will determine whether a patient is responding well or should be switched to another drug. This research model combines efficiency and flexibility, offering several treatment options (which is what we need in the real world), versus the more narrow and rigid designs of past clinical trials. 
  • Increasing use of electronic data and artificial intelligence: Have you made an online purchase lately? The enormous amount of data collection, storage and retrieval that supports those online purchases is our ‘new normal’ in shopping. But big data in medicine is a lot more complex. A major topic at the conference was how to partner, pool, and responsibly share data banks of patient information for the purposes of research. Sharing patient data allows us to advance science, accelerate precision medicine, and transform the care of IBD patients. Fostering collaboration helps to bring treatments to market faster, and assuring that patients get the care they deserve.

Putting all these factors together in new ways brings us to the cutting-edge in IBD research. For example, we now have several different drug classes to use in IBD. But we still don’t know when it is best to use which drug. Which drug class should be used first? Second? Third? And will that order of treatment be true for all people with IBD, or are there different patterns for different patients? Using pragmatic research with platform protocols may be the most efficient way to get this vital information quickly. And having large IBD data banks that can track thousands of patients over many years, such as the Foundation’s IBD Plexus® initiative, is critical for understanding long-term treatment outcomes. The collection of high-quality data is critical and can get us to a cure faster by accelerating research. The more data we collect from as many patients as possible, the more answers we can provide.

Getting the right patients into the right research studies 

Together with their partners, the Foundation is working on better research models and platforms to generate information that will apply to a wider range of IBD patients. And we’ll be able to build more studies into regular clinical practice.

But as patient advocate and clinical research coordinator Casey Jean Silvernale said at the conference, “Clinical trials don’t happen unless patients agree to participate.” You can read more about Casey Jean Silvernale in this blog post.

Sure, some obstacles to patient participation came from the rigid designs of traditional clinical trials. As we’ve seen, the new approach to clinical research should help solve a lot of those. But there’s still the crucial issue of making sure that patients have enough information, education, and support to make the best decisions for their own treatment.

Tina Aswani Omprakash had several discussions with her physician about a clinical trial before signing on to participate. Reflecting on her decision to enter the trial, Tina said:

“The key lesson for me was knowing that my doctors really do care and that we can make decisions together. They gave me no pressure, just lots of education. Many patients are scared to be guinea pigs. But we need to understand that we’re spearheading the future, taking the driver’s seat and being a partner in our own care. And we need to focus not just on possible side effects but also on the potential for new treatments to improve our quality of life.”

The power of working together

At the end of a very packed conference day, I had the opportunity to speak with the Crohn’s & Colitis Foundation's President & CEO Michael Osso and ask him for his takeaways from the conference:

“There were lots of great insights and ideas. And the good news is that much of it confirmed that we’re on the right track. But I was struck by a couple of things that I want to take back and think over with our staff.

First, the researchers were saying how hard it is to recruit patients into trials-- and we know that from our own experience. On the other hand, our patient stakeholders tell us that many patients do want to participate in trials. So, there’s a disconnect there, some gap that we need to further clarify and address. We’ve been trying to connect patients to clinical trials through our website, but we should try to find out what else they need to make those decisions.

Second, when we asked people for ideas on how to spend a million dollars—which is both a real question and a way of trying to tease out high impact ideas—I was struck specifically by how the ideas from patients and caregivers were so practical and geared towards improving quality of life.  It just underscored for me how crucial it is that we keep patient priorities front and center in our research focus.
Third, I think I heard more openness today about learning from, and partnering with, researchers in other related disease states. We’ve done some in that area, but I think there’s opportunity for more cross-research with other autoimmune inflammatory disorders, especially around treatments for fatigue, pain, and maybe mood issues. 

And finally, I’m impressed by how powerful it is to get everyone in the same room. Just hearing a surgeon talking about the need to be more connected to gastroenterologists to get the best patient care—I think I heard at least 10 comments like that in different ways. So, I deeply appreciate everyone coming here today to not only contribute but also listen to each other.”

This first-ever Foundation conference on clinical research strategies generated rich discussion and lots of ideas. Now they need to translate these ideas and suggestions into practical improvements and solutions. As they move forward, The Foundation will keep you updated in this as well as other areas. And if you have further questions or ideas for other topics you want covered in this space, send the Foundation an email at [email protected]   

Sheila Roher, MPH, is a science writer for the Crohn's & Colitis Foundation.