Table 1.

Pragmatic trial characteristics and design implications

Component	Characteristics	Implications
Eligibility criteria	Nonrestrictive in order to increase generalizability	Allows for rapid enrollment; longer follow-up is possible if trial duration is fixed
		Necessitates large sample size if nonselectivity reduces effect size
		Allows for EMR-based identification of participants
Intervention	Often already in widespread use	Sometimes allows for waiver or modification of informed consent
	Implemented by clinicians rather than researchers	Reduces required research infrastructure
	Can be implemented with flexibility	Effect size reduced if incomplete adherence and crossover between treatment groups
Control	Alternative to intervention that is also already in widespread use, or “usual care”	With usual care control, secular changes during trial conduct should be anticipated
Randomization	Often by cluster rather than individual participant	If cluster-randomization, sample size determination should incorporate:
	Treatment assignment usually not masked	Intracluster correlation coefficient
		Size of clusters; variability of cluster size
		Number of clusters
		If cluster-randomization, less potential for contamination across treatment groups but greater possibility of baseline imbalances across treatment groups
		If individual participant randomization, smaller sample size is required but sample may be less representative of population with condition
		Lack of masking allows for management by clinicians rather than research personnel
Outcomes	Often ascertained through electronic health records and/or administrative databases	Requires upfront attention to data specifications for outcome ascertainment
	Usually clinically important rather than intermediate or surrogate outcomes
Adverse event monitoring	Adverse events often ascertained through electronic health records and administrative databases	Can necessitate use of targeted rather than comprehensive adverse events

EMR, electronic medical record.