Abstract
The distinguishing characteristics of pragmatic clinical trials merits special attention when developing a monitoring plan. Pragmatic clinical trials are large in scope; participants are often identified from records or routinely collected data; investigators typically have less control over treatments or interventions; outcome data are often extracted from health records; and study activities are commingled with usual health care. We use lessons from The NIH Pragmatic Trials Collaboratory, which supports the conduct of 32 pragmatic clinical trials, to illustrate some of the challenges and solutions. Challenges include the complexity, quality, and timing of a real-world data pipeline; interventions that are embedded in clinical workflows; and the potential for incidental findings. We recommend regular, rigorous data quality checks, ongoing monitoring of adherence to interventions, and including someone who is knowledgeable about pragmatic clinical trials and novel research designs in the development of Data and Safety Monitoring Plans and Data and Safety Monitoring Boards. Close monitoring by study leaders, independent monitors or and Data and Safety Monitoring Boards is critical for a successful study that produces meaningful results. These experts must also decide about what evidence requires action and/or modification of the protocol and what information and thresholds would lead to a decision to pivot or terminate the trial.