NIH Collaboratory Rethinking Clinical Trials – The Living Textbook

Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials

Welcome to the Living Textbook of pragmatic clinical trials, a collection of knowledge from the NIH Health Care Systems Research Collaboratory. Pragmatic clinical trials are performed in real-world clinical settings with highly generalizable populations to generate actionable clinical evidence at a fraction of the typical cost and time needed to conduct a traditional clinical trial. They present an opportunity to efficiently address critical knowledge gaps and generate high-quality evidence to inform medical decision-making. However, these trials pose different challenges than are typically encountered with traditional clinical trials. The Living Textbook reflects a collection of expert consensus regarding special considerations, standard approaches, and best practices in the design, conduct, and reporting of pragmatic clinical trials. Given the rapid pace of change in this field, this electronic textbook will continue to be added to and updated.

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What is a

pragmatic clinical trial?


Engaging stakeholders

and building partnerships to ensure a successful trial


What is the

NIH Collaboratory?

NIH Collaboratory

By sharing lessons from our experience with pragmatic research, we aim to facilitate large-scale collaborative research studies with healthcare systems. The Living Textbook relies on the following knowledge sources:

trials that address questions of major public health importance and provide proof of concept for innovative pragmatic research designs.

CORES: Working groups that support the conduct of Demonstration Projects and generate guidance addressing implementation challenges.

DISTRIBUTED RESEARCH NETWORK: Network enabling investigators to collaborate in the use of electronic health data while safeguarding protected health information.

More about the NIH Collaboratory


  • September 21, 2017: New Article Highlights Generalizable Lessons Learned from the NIH Collaboratory In a new article in BMC Medical Research Methodology, Dr. Kevin Weinfurt and colleagues share generalizable lessons learned from the first four years of the Collaboratory and their experiences with the Demonstration Projects.  The authors highlight some of the challenges encountered and solutions developed and discuss remaining barriers and opportunities for large-scale evidence generation using ...
  • September 19, 2017: The NIH Health Care Systems Research Collaboratory Turns Five! Five years ago this September marks the birth of the NIH Health Care Systems Collaboratory, an NIH Common Fund project designed to build national infrastructure for conducting pragmatic clinical trials (PCTs). At the heart of the NIH Collaboratory is an ongoing series of Demonstration Projects that embed innovative pragmatic clinical research within the “real-world” conditions ...
  • August 25, 2017: NIH Collaboratory Launches New Website With Expert Insight on Pragmatic Trials Today, the NIH Collaboratory launched its new website, Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials. The updated website serves as the new home for comprehensive information about the NIH Collaboratory program, as well as a rich source of knowledge about special considerations for pragmatic clinical trials at each step of the research ...

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Promoting PRAGMATIC RESEARCH to increase the availability of high-quality medical evidence and IMPROVE patient care.


NIH Collaboratory Rethinking Clinical Trials – The Living Textbook: NIH Collaboratory Rethinking Clinical Trials – The Living Textbook. In: Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials. Bethesda, MD: NIH Health Care Systems Research Collaboratory. Available at: Updated September 21, 2017.