Conventional Explanatory Trials are conducted under tightly controlled conditions such as stringent eligibility criteria. This approach is often used for new drugs with limited safety data in early stages of development. However, these strict conditions can sometimes hinder enrollment and may not accurately reflect use of a drug in real-world care settings and patient populations.

Pragmatic Trials are designed in a manner where patient inclusion, therapy administration, and/or data collection aligns more closely with real-world clinical care contexts. For instance, pragmatic trials may be run without rigid eligibility criteria or be conducted through routine care visits. Pragmatic trials have more relevance to real-world care and populations, provide flexibility, enable diverse patient enrollment, and offer more generalizable study insights.

Hybrid Pragmatic Trials integrate traditional clinical trial methods with pragmatic elements to achieve targeted research objectives. In essence, they blend and harness beneficial aspects from both trial types to establish a more holistic, flexible, and efficient approach.

FDA has emphasized an interest in pragmatic trials in recent years through its initiative Project Pragmatica.