About Pragmatic Clinical Studies

We launched our Pragmatic Clinical Studies (PCS) initiative in early 2014 to expand our support of high-priority, patient-centered comparative clinical effectiveness research, or CER, projects. These large-scale, real-world trials and observational studies address critical questions faced by patients, caregivers, clinicians, and healthcare delivery systems.

As of Spring 2022, our Board of Governors had approved about $530 million to fund 48 Pragmatic Clinical Studies.

We created this funding category in response to both stakeholder feedback and our understanding that many key health research questions require a greater investment and longer timeline than our previously established broad funding announcements allow.

High-priority research questions for PCS awards came from several sources. These included topics listed in the 2009 Institute of Medicine Priorities for CER report, the Agency for Healthcare Research and Quality’s Future Research Needs Projects, as well as topics recommended by patients and other stakeholders through PCORI’s topic prioritization process. All PCS funding announcements included a list of such PCORI priority topics. In addition, our PCS funding announcements called for the research community’s best ideas for other high-priority topics.

PCS announcements appeared three times a year; applicants could request up to $10 million in direct costs. Applicants had to provide a letter of intent, or LOI, and we invited approximately 50 percent of them to submit a full application.

Answering High-Priority Questions

The title of our initiative emphasizes that we seek pragmatic studies appropriate for a specific high-priority question. Answering that question must be of great practical value for healthcare decision making, and study findings should reflect everyday care for a wide range of patients. These studies usually take place in real-life practice settings, such as a typical hospital or clinic, and include diverse patients with different needs, circumstances, and preferences. In contrast, traditional clinical studies tend to look at how well care approaches work under ideal conditions, with highly selected patients, in specialized research centers.

​Like other research we fund, pragmatic projects measure benefits and harms to determine which of two or more healthcare options works best for different types of patients. Studies can compare, for instance, drugs, devices, procedures, or delivery-system interventions. All projects must address the range of health outcomes that are meaningful to the patient population under study. These studies often have large sample sizes—sometimes thousands of participants—so they can detect potential differences in effectiveness and outcomes in groups of patients with specific characteristics, an approach known as heterogeneity of treatment effect.

We attach high importance to getting the research question right to ensure that important results influence practice and are likely to transform health care nationwide. To do this, we insist that patients, clinicians, and other healthcare stakeholder groups (e.g., payers, purchasers, policy makers) must be meaningfully involved throughout the research process. We typically expect that relevant organizations (e.g., patient groups, specialty societies, or insurer groups) will participate. We are happy to facilitate contact between successful awardees and such organizations.

Guidance on the Design and Conduct of Trials in Real-World Settings: Factors to Consider in Pragmatic Patient Centered Outcomes Research

Comparative clinical effectiveness research is commonly performed in real-world settings that require thoughtful planning to balance the extent of experimental control with more naturalistic (or "pragmatic") study conduct. Applicants for PCORI funding and PCORI awardees should refer to this guidance for important factors in weighing whether and how pragmatic research features best serve the study question and purpose.

View/Download this Guidance

Pragmatic Clinical Study Spotlights

To date, our Board of Governors has approved more than three dozen PCS projects selected on the basis of their design and following characteristics:

• An examination of the benefits and harms of different interventions and strategies that are delivered in typical clinical and community settings
• A comparison of at least two alternative healthcare approaches
• An examination of interventions such as specific drugs, devices, and procedures, as well as medical and assistive devices and technologies, behavioral change, complementary and alternative medicine, and delivery-system interventions
• Broadly representative patient populations
• A comparison of health outcomes that are meaningful to the patient populations under study
• Enough participants to provide precise estimates of hypothesized differences in effectiveness and to support evaluation of potential differences in patient subgroups

View a list of PCORI-funded Pragmatic Clinical Studies

As with all PCORI projects, these studies were approved by our Board subject to a business and programmatic review by PCORI staff and completion of a final research contract.

Posted: August 1, 2016; Updated: March 1, 2022