1. Pragmatic Trial Designs
Cathleen Colon-Emeric, MD, MHS
Jane Pendergast, PhD

3. Complex Interventions often fall on the “Pragmatic” end of Spectrum

4. 3 General Design Categories
Individually Randomized Trial
Individually Randomized Group Treatment Trial
Group Randomized Trial (a.k.a. Cluster Randomized Trial)
Match Game
Inouye Hospital Elder Life Program
Allen Group PT for OA Trial
Edinger CBT for Primary Insomnia Trial
Tinetti Fall Prevention Program
Tannenbaum EMPOWER Benzodiazepine Deprescribing trial

5. Issues with Groups Chance of confounding: IRT<IRGTT<GRT
Impact of within-group correlation
Extra variation attributable homogeneity within groups and variation among groups (=ICC=intraclass correlation coefficient)
Increased type 1 error rate
Increased sample size for same power
More complicated analysis approaches that account for clustering
Time as a factor
Post-test only
Pre-post test
Extended designs

6. Group Membership Can Change over Time
Nested Cohort
Nested Cross-Sectional

7. Additional Threats to Validity in GRTs
Approaches
Selection
Differential history (external influences)
Differential maturation (members change at different rate by group)
Contamination
Matching/stratification or Constrained allocation
Predict, measure
Matching, pre-post designs
Careful group selection, withhold key resources

8. Other Cool Designs to Consider
Adaptive Trials
Group Sequential/Stepped Wedge
Discontinuity
Preference Trials
Platform Trials
Sequential Multiple Assignment Randomization (SMART)/ Dynamic Treatment Trials

9. Adaptive Trials
Pre-planned modifications to the trial based on data accumulating during the study
Revise sample size
Drop an intervention arm
Adaptive randomization
Enrichment designs - change recruitment criteria to focus on subgroups particularly benefiting
Require interim analyses and type 1 error penalties
Some adaptations are still controversial; may impact integrity and validity of the study.

10. Example: Platform Trials
Efficiently evaluate multiple treatments/combinations in heterogeneous populations
Disease not treatment is the focus

11. Multiple Baseline Design

12. Stepped Wedge
Need to roll out groups over time for policy or logistical reasons

13. Discontinuity Trials
Unethical to randomize

14. Preference Trials
Patient preference for treatment may lead to selection or performance bias

15. SMART and Dynamic Treatment Trials
Real-world practice dynamic and changes by patient adherence/response
Identify optimal treatment algorithm

16. Designing a Pragmatic Trial
Before you decide to design a pragmatic trial, it is always a good idea to talk with someone who has implemented one similar to what you are proposing.
The term “pragmatic” implies that you will have some constraints to work around (as compared to an individually-randomized trial) that can be difficult to maneuver.
Analyses of the data from these trials can be more difficult, and suffer more from issues such as missing data/dropout/changes in environment, etc.