Keywords: Pragmatic Clinical Trials, Randomized Clinical Trials,
Frank W. Rockhold, PhD Professor of Biostatistics and Bioinformatics Duke Clinical Research Institute Duke University Medical Center
The concept of pragmatic clinical trials (PCTs) dates back to the 1960s (Schwartz and Lellouch, 1967). Many “large and simple” trials conducted in 1980s and 1990s in cardiovascular disease can be considered as PCTs. These principles have recently been outlined in the PRECIS guidelines (Thorpe, 2009 and Loudon 2015) which will be reviewed and contrasted with the standard “RCT” approach. Current PCTs are primarily designed to compare strategies for the prevention, diagnosis and treatment of diseases, sponsored by health institutes such as the Patient-Center Outcome Research Institute (PCORI). The largest PCORI example to date is the ADAPTABLE trial comparing high and low dose aspirin in 20,000 patients (Johnston, 2016). Additionally, there is a growing use of cluster randomization in PCT’s. PCTs have been considered for the marketing authorization application of new drugs with an increasing regulatory attention to using real world evidence in drug approval. GSK’s Salford Lung Study (New et al, 2014) was the first phase III pragmatic clinical trial supporting registration of the new drug. All of these will be reviewed as examples of PCT’s and contrasted with the “standard” approach and the intent of the PRECIS guidelines. Finally, the role of PCTs in the evaluation of safety will be discussed.