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Table 2 Design features of pragmatic trials that influence data and safety monitoring plans

From: Principles and procedures for data and safety monitoring in pragmatic clinical trials

Design features intended to increase generalizability and/or efficiencyEffect on data and safety monitoring procedures
Enrollment of all eligible patients in a defined clinical populationRecruitment or enrollment rate is more predictable
More vigorous advertising or outreach is less likely to increase enrollment
Cluster-level randomizationStatistical power is influenced by within-cluster correlation of outcomes
Monitoring enrollment may include monitoring of cluster size and within-cluster correlation
Safety profiles of study treatments may already be establishedBetween-group comparisons to establish safety or risks may be less useful
Treatments often delivered by community providers, with little direct involvement by investigatorsFewer data available regarding adverse events or relationship between events and study treatment
Investigators may have less ability to monitor or assure safe delivery of study treatments
Frequency of contact with study staff may vary between treatment groupsComparison of adverse event rates between treatment groups may be biased
Fidelity of or adherence to treatments may be variableRelationship between adverse events and study treatments may be more difficult to evaluate
Valid inference may require some monitoring of (and corrective actions to improve) fidelity or adherence
Potential adverse events often ascertained from health system recordsIdentification of adverse events may be significantly delayed
Study outcomes often ascertained from health system recordsChanges in health system record-keeping may affect integrity of study data
Delays in access to records data may interfere with interim analyses of study outcomes
Study questions may involve wider range of outcomes, such as effects on health service use or costLonger follow-up periods may be necessary to assess some “downstream” outcomes of study treatments
Study questions may focus on implementation or policy, rather than individual clinical decisionsDecision thresholds for early termination of enrollment or intervention delivery may be asymmetric with respect to evidence for benefit or harm