Project Summary

One of PCORI’s goals is to improve the methods that researchers use for patient-centered outcomes research. PCORI funds methods projects like this one to better understand and advance the use of research methods that improve the strength and quality of comparative effectiveness research.

This research project is in progress. PCORI will post the research findings on this page within 90 days after the results are final.

What is the project about?

Randomized clinical trials are a type of research study that test how effective and safe treatments are. But new treatments may work differently in real-world settings than they do in research studies. To understand how well new treatments work in real-world practice, researchers may use a hybrid study design. Hybrid designs combine information about treatments and outcomes from clinical trials with real-world data on patients who receive the treatment.

In this study, the research team is focusing on two issues that are important when using hybrid designs. First, the kind of patients who usually receive a treatment may be different from patients who take part in trials. Patients who use a treatment may also change over time. Second, the way doctors prescribe treatments often differs from the way researchers test treatments in trials. For example, doctors might prescribe a different dose of a medicine or prescribe treatment for a different length of time. The team is trying to improve the design of hybrid studies by developing methods that account for these two issues.

How can this project help improve research methods?

Results may help researchers make better use of hybrid studies to understand the way treatments work in real-world practice.  

What is the research team doing?

The research team is developing new methods to design and analyze hybrid studies. The methods account for factors such as patients’ age, medical history, and treatment plan to update what is known about the benefits and harms of a new treatment from clinical trials. The team is testing the new methods using data from a study that compared two chemotherapy treatments for colon cancer. Finally, the team is developing guidance for researchers on how to use the methods.

Patients, doctors, insurers, healthcare systems, and drug regulators are giving feedback on this study.

Research methods at a glance

Design Elements Description
Goal To develop guidance and analytical methods for designing and analyzing hybrid study designs to characterize differences in demographic and clinical characteristics and therapy adherence patterns between trial and various target populations (e.g., trial eligible, approved indication, and treated populations) and estimate treatment effects that reflect care delivered in clinical practice 
  • Testing the new methods with data from a randomized clinical trial involving two chemotherapy treatments for colon cancer and data from electronic health records from a large community oncology network
  • Using quantitative measures and data visualizations to characterize differences in clinical trial and clinical practice populations
  • Using the weighted parametric g-formula to compare the effectiveness and safety of adjuvant chemotherapy options under varying adherence scenarios

Project Information

Jennifer Lund, PhD
University of North Carolina at Chapel Hill
Enhancing Hybrid Study Designs for Comparative Effectiveness Research

Key Dates

August 2018
October 2023

Study Registration Information


Award Type
Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
State State The state where the project originates, or where the primary institution or organization is located. View Glossary
Last updated: January 20, 2023