Proving the Concept: Moving Ahead with PCORnet's First Clinical Trial

We’re pleased to report taking a major step toward test-driving PCORnet, the national patient-centered clinical research network designed to enhance the nation’s capacity to conduct studies that will answer important questions faced by patients and clinicians.

It’s been 10 months since we launched PCORnet, a large “network of networks” designed to allow clinical outcomes research to be conducted in real-world settings faster and at lower cost than is possible now. Since then, the partner networks that make up PCORnet—11 large health systems and 18 networks run by patient groups and their clinical research partners—have been getting ready to put the project to the test.

That process is now under way. Our Board of Governors recently approved a topic for PCORnet’s first, pilot trial— studying the optimal dose of daily aspirin needed to lower the risk of heart attack and stroke in patients previously diagnosed with coronary artery disease (CAD). Now we’ve issued a limited PCORI Funding Announcement (PFA) soliciting a multi-network research plan designed by the PCORnet partner networks with patients and relevant experts. We’ll evaluate the submitted proposal through our merit review process. We plan to provide up to $10 million in funding for direct costs for one trial of up to three years.

We look at this first randomized trial as a chance to evaluate and refine PCORnet’s data and clinical trials infrastructure. Investigators must use efficient recruitment strategies to ensure broad representation from the patient community in the trial; we expect the study will follow thousands of patients in order to determine whether there are clinically meaningful differences in the effectiveness and safety of two commonly prescribed doses of aspirin. To be successful, the study also must engage patients, clinicians, and health system leaders throughout the research process to capture relevant patient-centered outcomes from real-world clinical settings and optimize data collection across networks. And we’re requiring researchers to have clear management and analysis strategies and develop a dissemination plan, so they’re ready to help get the study results out to those who can use them.

Because this trial is a demonstration project that is part of PCORnet’s Phase I development, we are limiting applications to the current PCORnet partner networks. By the end of Phase I, PCORnet will have established guidance for how the infrastructure can be used by current partners and other researchers.

Why an Aspirin Trial?

Assessing the best dose of aspirin for patients with CAD is an ideal topic for the first PCORnet study. A definitive answer is likely to impact the way more than 15 million Americans with this condition are treated. The outcomes addressed are important to patients, the clinicians who care for them, and the healthcare system as a whole. Given the high prevalence of CAD, it’s crucial to minimize its complications, including recurrent heart attacks and thrombotic strokes, but it’s also critical to make certain that our attempts to do so don’t cause complications of their own. In the case of aspirin therapy, it’s clear that daily aspirin reduces recurrence of disease in patients previously diagnosed with CAD. But aspirin therapy can also lead to life-threatening bleeding, both intracranial as well as major gastrointestinal. The higher daily dose (325 mg, or full dose) commonly prescribed likely has more adverse effects than the lower dose (80 mg, also called baby aspirin). Previous trials have produced conflicting evidence about the magnitude of potential benefits and risks of different aspirin doses. Reflecting that uncertainty, about half of US patients with CAD take a full-dose aspirin daily, the others a lower dose.

Effects of aspirin dosage in CAD patients is an investigational topic particularly suitable for PCORnet. Electronic health records that are a part of usual care within the participating healthcare systems can readily identify the eligible patients and the relevant outcomes—heart attacks, strokes, and gastrointestinal bleeding. All this work will be done under rigorous data security, privacy, and informed consent standards.

Last March, we asked researchers, patients, and other stakeholders from the PCORnet research networks to propose topics for this first interventional trial. We prepared briefs describing the most promising suggestions. Two groups—current PCORnet Principal Investigators and PCORI’s Advisory Panel on Assessment of Prevention, Diagnosis, and Treatment Options—prioritized the topics. Both groups gave top ranking to optimal maintenance aspirin dose for patients with CAD. On July 29, our Board approved this as the topic for the first PCORnet clinical trial.

We were especially pleased to find a topic for which data collections can be seamlessly integrated into routine clinical operations and minimize disruption to participants’ daily routines.

Now What?

Once the PCORnet networks submit their proposal or proposals, we will conduct a rigorous review by a panel that includes clinical experts on coronary artery disease, methodological and statistical specialists, patient representatives trained in review of scientific proposals, and representatives of other stakeholder groups. In both a preliminary evaluation and an in-person discussion, the review panel will consider technical merit, patient-centeredness, and patient and stakeholder engagement. The panel will identify strengths and areas for improvement.

After the panel assigns scores, PCORI staff will determine whether to recommend a proposal to our Selection Committee, which is made up of members of PCORI’s Board and Methodology Committee. The full Board will then vote on the selected proposal. The awardees will refine their research protocol by working with a subcommittee of PCORI’s Advisory Panel on Clinical Trials that may also include participants from the merit review panel. We expect work on the trial to begin next spring.

We look forward to this exciting opportunity to take advantage of PCORnet’s capability to advance rapid and efficient research. We expect the trial will test the operational, logistical, and collaborative processes that will improve the efficiency of future PCORnet studies. Finally, we expect the study will demonstrate the value of PCORnet’s approach and make a major contribution to answering a clinical question of major importance to patients and those who care for them.

We’ll report back to you regularly on our progress.