Newswise — DURHAM, N.C. – The Duke Clinical Research Institute is launching an ambitious new project that is intended to answer a question of considerable clinical importance, while also changing the way pragmatic clinical trials are conducted.
The Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) study will assess whether low- or standard-dose aspirin is better for preventing heart attacks and stroke in patients with coronary artery disease.
The study will be the first randomized clinical trial conducted for PCORnet, the National Patient-Centered Clinical Research Network, and will serve as a test of the network’s scope and capabilities. PCORnet is an initiative of the Patient-Centered Outcomes Research Institute (PCORI), an independent, nonprofit organization authorized by Congress in 2010 to fund research that will provide patients, their caregivers and clinicians with the evidence-based information needed to make the better-informed healthcare decisions.
“This will be one of the largest pragmatic randomized clinical trials that has the potential to have a huge impact on the outcomes of patients with heart disease,” said the DCRI’s Adrian Hernandez, M.D., MHS, co-principal investigator of PCORnet’s Coordinating Center. “It will also change how we conduct large clinical trials by employing novel methods to identify, recruit and follow up patients electronically.”
More than 15 million Americans have coronary artery disease, and current American College of Cardiology/American Heart Association guidelines recommend aspirin at a dose of 75 to 325 mg once daily for patients with a history of heart attack.
Yet despite dozens of clinical trials, the optimal dose of aspirin for these patients — one that will provide the best balance between maximizing cardiovascular protection while minimizing bleeding — remains unclear.
“Answering the simple question on the right dose of aspirin for patients with heart disease could have a profound impact on health care because we’re looking at a widely used therapy that isn’t completely understood,” said the DCRI’s Matthew Roe, M.D., MHS, who is ADAPTABLE’s co-principal investigator.
Although most studies have found that lower-dose aspirin is associated with less bleeding, these studies have provided contradictory evidence regarding the comparative effectiveness of low versus standard-dose aspirin in reducing ischemic events such as heart attacks or strokes.
ADAPTABLE is designed to provide a definitive answer to this question. In the study, 20,000 patients who are at high risk for ischemic events will be randomly assigned in a 1:1 ratio to receive an aspirin dose of either 81 mg per day or 325 mg per day. Researchers will conduct follow-up centrally for up to 30 months via a patient web portal or by telephone and by PCORnet’s data platform. ADAPTABLE is scheduled to launch in the fall of 2015.
ADAPTABLE’S rationale goes beyond investigating the clinical question of aspirin dosage. The investigators will also use the trial to test a number of innovative tools and techniques they hope will improve the infrastructure for conducting randomized clinical trials in the United States.
“The biggest challenge is getting people to change how they’re used to doing trials,” Hernandez said. “What we’re attempting is something that hasn’t been done before in the world of clinical trials.”
One unique aspect of the project is the role that patients and patient advocates will play. Patients will be involved at multiple levels during the trial’s active and follow-up phases: Each participating network will have one patient on the study’s steering committee. ADAPTABLE will also use a patient-powered consent and randomization process. Each participating research network will identify several thousand patients to approach by email. If patients are interested in the trial, they will use the Internet to consent and enroll themselves in the study. ADAPTABLE’s coordinating center will have a patient representative, Bray Patrick-Lake of the Clinical Trials Transformation Initiative, on its steering committee.
“It’s novel for a large, pragmatic trial to have patients engaged at the inception of the research question and to have legitimate influence over the design and conduct of the study,” Patrick-Lake said. “I believe this has produced not only a better protocol, but many opportunities for co-learning between researchers and the patient community.”
ADAPTABLE’s architects hope their work will help them find new ways to leverage PCORnet’s existing networks, particularly in the follow-up phase of the study. One such innovation is the use of a common data model (CDM) for the patients’ electronic health records (EHRs). The CDM is a tool for organizing patient data from different EHR systems into a standard structure.
“Each of the participating networks includes EHR systems that we will be using as data sources for ADAPTABLE,” said Lesley Curtis, Ph.D., co-chair of PCORnet’s Data Standards Task Force and the DCRI’s director of the Center for Pragmatic Health Systems Research. “The CDM allows us to organize shared data elements in each system, so that each network can answer research queries much more quickly.”
“Much of this is a work in progress,” Curtis said. “But we’re optimistic that we can demonstrate the value of PCORnet’s infrastructure and methods with this study.”“ADAPTABLE will challenge each of us to move away from the traditional ways trials are done,” said Lisa G. Berdan, PA, MHS, DCRI’s director of MegaTrials. “We’re as excited about the operational methodologies we will be testing as we are about the important clinical question. We expect to develop new knowledge about clinical trial operations and will share this knowledge with the clinical trial community.”
Another unique aspect of ADAPTABLE is the use of centralized processes for institutional review board approval. This approach, recently endorsed by the National Institutes of Health, is intended to streamline the approval process.
“ADAPTABLE opens a new era for highly pragmatic trials directly connecting with patients and built off of a reusable research infrastructure,” said Eric Peterson, M.D., MPH, DCRI’s executive director. “It’s an innovative way to do research and we’re very excited DCRI is leading the way.”
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