Coordinating Research with 80 Million Participants: A PCORnet Q&A

No question, discovering new treatments and cures for diseases is a critical task for medical research. But many patients and families stand to benefit just as much or more from understanding which existing therapies work best for whom.

Christopher Forrest, MD, PhD, a professor of Pediatrics at The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, recently took on a new and influential position to help shape such comparative-effectiveness research at the national level. As newly appointed chair of the research committee for the national patient-centered clinical research network called PCORnet, he is helping research studies take shape to include a participant population of up to 80 million Americans who are part of 33 large research networks.

Dr. Forrest was already principal investigator of one of these component networks, PEDSnet, which brings together data from eight children’s hospitals including CHOP to accelerate discovery in pediatric clinical research.

On the occasion of this new appointment, Cornerstone sat down with Dr. Forrest to learn more about how these research networks are accelerating discovery, and why that is so important. The edited conversation follows below.

What are the fundamental problems in medicine and research that PCORnet is intended to solve?

We believe that the healthcare clinical research system has been failing the people who pay for it. Research occurs way too slowly. It is very challenging to get a study off the ground, get all the contracting, get your institutional review board approval, particularly so for multi-site studies, and then to start recruiting patients. The complexity of the work is very high. Plus, I just learned that the results from one-third of all clinical trials funded by the National Institutes of Health are never published. In pediatrics, we have the added problem of hand-me-down research. The research tends to exclude children, and we use results from adults for kids.

How does PCORnet aim to solve these problems?

PCORnet’s goal is to transform the clinical research infrastructure to make research faster, cheaper, and better.

Faster means that from the moment the project starts to when the first patient is enrolled is a shorter period of time. It means that recruitment is done more quickly. It means that, once results are available, they’re disseminated more rapidly. By moving faster, that leads to less expensive clinical research, and that means you can do more. By “better” we mean we want to be doing research that provides information to patients and clinicians that they can use to make better healthcare decisions.

PCORnet’s sweet spot is taking existing treatments and understanding how well they work in the real-world population. A lot of times decisions are made based on gut feelings or based on physicians’ practices that were handed down to them from their teachers, and there may not be good research that underpins them. Clinical trials that show a medication actually does work, don’t take account of all the diversity we have in patient populations. PCORnet, with 80 million people, is able to address that diversity.

We also have a very strong patient engagement component, so that research participants are a part of the design of studies, their conduct, and their dissemination and implementation.

What kind of research is being done, or could be done, through PCORnet and its component networks including PEDSnet?

The key type of research is what we call pragmatic research, both observational studies and clinical trials.

PCORnet’s flagship clinical trial is called ADAPTABLE. It asks a pretty simple clinical question: What is the right dose of aspirin to take to prevent heart attacks? We know that aspirin can help prevent heart attacks, but it has its side effects. Should you take a baby aspirin, which is like a quarter of a regular aspirin, or should you take full strength? There is lots of variation across hospitals in the recommended dose, and there’s no evidence to guide decision-making around the right dose of aspirin.

A key attribute of PCORnet studies is that we can use electronic means to contact, enroll, and engage with patients, and to collect a lot of the outcomes data. Patients enroll and go through the informed consent process online, and their electronic health records are linked into the research.

This approach is efficient, rapid, and cost-effective. We’re enrolling 20,000 people to run the ADAPTABLE study in 24 months, at a cost of $850 per participant. Other large cardiovascular clinical trials cost multiple thousands of dollars per participant.

We have a second study that I’m actually one of the leaders on, looking at the effects of antibiotics on children’s growth. We published a paper that showed at CHOP that antibiotics were associated with children’s growth. Now we’re doing a much larger study to really understand this phenomenon better.

How did PCORnet come about, and how is it organized?

PCORnet is the flagship program of Patient-Centered Outcomes Research Institute (PCORI), an independent nonprofit organization that was congressionally authorized through the Affordable Care Act to improve the quality and relevance of information available to help people make informed health decisions. It is one of the shining examples of what we can do through Obamacare. PCORnet is one of the largest initiatives among a number of national efforts that are coalescing to produce a national evidence generation infrastructure.

PCORnet was launched in 2014 and has grown to include 13 clinical data research networks like PEDSnet, and 20 patient-powered research networks (PPRNs). These include a variety of types of networks. While PEDSnet is focused on pediatric populations, other networks have different ways of cutting across patient groups in all types of healthcare research. For example, CAPriCORN brings together all the research institutions in Chicago, in a way designed to understand and address health inequities within a region.

In the CHOP/Penn community, we have leaders of three of these networks. I lead PEDSnet. Kathleen Sullivan, MD, PhD, at CHOP, leads one of the PPRNs focused on immunodeficiency. In addition, Peter Merkel, MD, MPH, the chief of rheumatology at Penn, runs a PPRN focused on vasculitis.

I’m the elected representative of the 33 networks to lead the research committee, one of three leadership committees in PCORnet.

What does the research committee do for PCORnet?

The role of the research committee is to stimulate new large-scale research projects like ADAPTABLE. Our goal is to facilitate new research and to make bringing a research project to PCORnet easy and pleasurable.

PCORnet is opening its doors for new research ideas this spring. There are three types of inquiries that people can make.

One, for the purposes of planning a study, they could ask PCORnet to do a query of its database, to tell them how many patients have a particular disease or meet particular criteria for a clinical trial.

Two is a type of inquiry you could call matchmaking: Let’s say that you are a parent who runs an advocacy group for children with complex congenital heart disease, and you would love to see a study done on the quality of life of children with complex heart disease. You can contact PCORnet to ask, “Is this the kind of project that someone in the network would do?” We would determine if there’s interest, and, if so, form a team.

In the third kind of inquiry, you could suggest a study that would be a great study for PCORnet, and we help you set up your study.

All of these queries can be submitted through the website portals for both PEDSnet and PCORnet. Soon, we will make a soft launch of this functionality. June is the formal launch.

As research committee chair, I’ve also set up something called collaborative research groups to facilitate the creation of large research projects. This is a structure that crosses all the networks within PCORnet in order to focus on particular areas of interest, like cancer, heart disease, diversity and disparities, autoimmune and immunologic diseases, neurologic diseases, and pediatrics.

The value of this is that, for example, through the pediatric collaborative research group, we think we can tap into 20 million kids. Up to 25 percent of all U.S. children could potentially be contacted in one way or another through this group. This is valuable because some pediatric disorders or healthcare events occur so infrequently that even with eight institutions in PEDSnet, that might not capture enough patients to answer certain questions.

More information about PCORnet is available on the PCORnet website.

See other Cornerstone posts about Dr. Forrest’s work with PCORI and PEDSnet here.