Methods and New Approaches in Pragmatic Trials

1. Course Aim

Pragmatic randomized clinical trials (pRCTs) are trials conducted in a routine clinical practice setting with minimal disruption to clinical health care (other than randomization) to assess effectiveness and safety of interventions. They require the expertise of pharmacoepidemiologists who understand considerations and methodologic challenges that arise with generating and analyzing real world data compared with traditional “explanatory” RCTs.

The course will cover fundamentals of pragmatic trial study designs and methods of analysis, as well as approaches for ensuring the generation of robust real-world evidence. Leveraging electronic health records and other sources of RWD to improve efficiency of pRCTs and support embedding of pRCTs in health care delivery settings will be addressed. Operational challenges and lessons learned from conducting pRCTs will be shared along with case examples from PCORI and other invited speakers.

2. Requisites Statement

Entry level, though familiarity with basic principles of observational and/or experimental study design and statistical methods is recommended. Recommended pre-course reading material will also be provided.

3. Course Objectives

• To understand key design considerations for pRCTs and drivers of design choices
• To understand statistical issues for the analyses of pRCTs
• To understand considerations pertaining to primary data collection vs use of secondary data sources
• To identify and address operational considerations and challenges in implementing pRCTs
• To gain insight into current and recent pragmatic trial case examples with regard to their methods, implementation, operational challenges, and intended use as real-world-evidence

4. Syllabus Outline

1. Overview of Pragmatic Trials-J Christian
To introduce attendees to the rationale and context for conducting pRCTs, present different design tools for researchers, share pivotal studies and articles, and recent examples of impact with various stakeholders.

2. Study designs for pragmatic trials – P Velentgas
The following topics related to study designs for pragmatic trials will be addressed: patient-level and cluster randomized designs, cross-over trials, platform trials, blinding, inclusion and exclusion criteria, choice of comparators, and data collection with emphasis on trials that blend primary data collection with EHRs or other secondary data.

3. Statistical analyses for pragmatic trials – C Girman
Analytic methods related to pragmatic trials will be reviewed, including different considerations related to randomization, sample size estimation for cluster randomized and stepped wedge designs, appropriate analysis methods, and non-inferiority vs. superiority hypothesis testing.

4. Recent case examples of pragmatic trials funded by PCORI – A Trontell
Dr. Trontell will provide an overview of some of the recently completed PCORI-funded pragmatic trials, focusing on unique features of PCORI’s approach and challenges of implementation. Investigator feedback on challenges in pragmatic trials and a patient-centered approach to design of such trials will also be given.

5. Additional featured case example of a pragmatic trial, TBC