Following the presentation of results from DCRI’s ADAPTABLE Study at the recent American College of Cardiology Scientific Sessions, we spoke with DCRI’s Executive Director, Adrian Hernandez, MD, MHS, a contributor to ADAPTABLE since its inception in 2015. ADAPTABLE sought to determine the safest and most effective dose of aspirin for patients with existing cardiovascular disease. Hernandez discusses learnings from the landmark study, ranging from clinician takeaways to electronic health record (EHR)-enabled research and participant engagement in clinical trials.
How should clinicians interpret the results of the ADAPTABLE study as they move forward in prescribing aspirin for secondary prevention?
ADAPTABLE provides an answer for a question that has been posed for decades: What’s the right dose of aspirin in patients who have heart disease? You would think that for something that’s been available over the counter for decades, we would have a full understanding about aspirin and its tolerability.
What the study showed is that the dose you’re on is most likely the right dose.
There were no major differences in clinical outcomes between the low dose of 81 mg or the higher dose of 325 mg. For patients who are taking 81 mg, staying on the low dose makes a lot of sense. On the other hand, if you’re tolerating 325 mg, then that makes sense in terms of continuing. For patients starting aspirin or resuming aspirin, starting on the lower dose is probably right because it’s easily tolerated.
To speak further to tolerability—even though it wasn’t an endpoint of our study, we came across some interesting findings. It’s been known that different doses of aspirin may affect tolerability, because they produce varying side effects. We found in ADAPTABLE that a lot of people switched from 325 mg to 81 mg of aspirin. That could be because 81 mg is more easily tolerated, or it could be because clinicians or patients prefer the lowest dose that they need. It’s likely a variety of reasons, but a lot of people did switch from 325 to 81 during the course of the study.
What made now the right time to design a study to answer this question?
With ADAPTABLE, we were aiming for two goals. One was to test an important question about aspirin that affects literally millions of people, and the other was to use a new infrastructure that takes advantage of electronic health records (EHRs), which patients generate every day, to conduct a more efficient trial.
That new infrastructure was PCORnet®, the National Patient-Centered Clinical Research Network, which is a national resource of health care systems and networks. ADAPTABLE really was the first large pragmatic trial using PCORnet. We structured ADAPTABLE to function pragmatically within the PCORnet environment, efficiently leveraging existing EHR data. Generating new study-specific data would have taken more time and more money.
Tell us more about the ideas behind PCORnet—both its formation and what it has contributed to research so far.
A number of years ago there was national investment in creating a national network of EHRs with the goal to improve quality of care. In addition, clinical researchers can layer EHR data onto clinical trials to accelerate the studies.
But across the country, every health system works with a different EHR system. That’s where PCORnet comes in. As the coordinating center for PCORnet, the DCRI has helped to establish a common data model, so that information from different EHRs can be used for the same research project.
For ADAPTABLE, the study team relied on a common data model to generate answers for the ADAPTABLE questions. With the EHR data made available through PCORnet, we identified people who were eligible to participate in the study and were able to understand outcomes more quickly as study results came in.
We also learned that clinical researchers cannot rely on EHR data alone. We also have to get information directly from participants to understand how they describe their health, and we have to ensure that we link to other data sources, such as claims data. Using multiple data sources is important to help understand the complete picture of someone’s health.
What role does the DCRI play in PCORnet’s success as the PCORnet coordinating center?
For over a decade people have realized that our research ecosystem doesn’t always generate the answers that people want, as quickly as people want, or at the most efficient cost. PCORnet was formed to try to fill these gaps.
The DCRI is fortunate to serve as the coordinating center. We unite various health care systems and networks within PCORnet with the data that is the foundation of PCORnet; we also bring other parties to the table by engaging participants and other stakeholders. Through these activities, we help to shape not only the foundation and functions of PCORnet, but also the questions that are addressed through the network.
DCRI also brings our 25-plus years of experience in clinical trials and observational studies to our role. We use the breadth of our experience in order to help understand how the research ecosystem can leverage PCORnet to answer the most important questions more efficiently, to deliver data in a timely way, and then, ultimately, to implement evidence into clinical practice.
Earlier in our conversation, you mentioned getting information directly from research participants. Can you explain how ADAPTABLE incorporated the perspectives of research participants in novel ways?
Participant engagement was a centerpiece for ADAPTABLE. It began with selecting the study question; over two dozen questions were identified as possibilities for an initial demonstration project for PCORnet. We selected the question with and for patients—and we ultimately came up with, “What’s the right dose of aspirin?”
We then created a forum of patients who informed every decision made along the way, whether it was the consent form, or how we presented the study to the public, or how we return results to the community of people who participated in the study. That group named themselves the Adaptors, and they’ve been the trial’s heart and soul.
The Adaptors reminded us that it’s not just about them—it’s actually about the 15,000 participants in the trial, and the millions of people with heart disease. So we made an effort to communicate to study participants and the public through different forums, such as Facebook Live, or blogging, or posting the protocol publicly and getting comments.
What do you see for the future of PCORnet and EHR-enabled clinical research?
COVID-19 has underscored that we need to have a more robust research ecosystem—a platform, if you will—that can continuously deliver answers through clinical trials and observational studies. What we see for the future of PCORnet, through programs like ADAPTABLE, is starting at a foundation of health care systems, where data is generated every day through people engaging directly in their clinical care.
As we move forward with PCORnet, we will gain a better understanding of how to engage people—how to help them decide if they want to participate in research, which answers they want to contribute to, and how we can conduct research more simply, even from their homes.
The last thing is, how do we scale clinical research studies so that we’re answering multiple questions for multiple groups of people? We need to create a virtual cycle that generates answers for everyone and, over time, returns those results to the communities—and then ultimately implements those results into everyday life.