1. PRAGMATIC Study Designs: Elderly Cancer Trials
Karla V. Ballman
Alliance Cancer in the Elderly Statistician
Mayo Clinic
May 2015

2. What is a “Pragmatic” Trial?
Concept introduced by Schwartz and Lellouch, 1967
Contrast between “explanatory” and “pragmatic” trials
explanatory trial purpose: answer a scientific question
pragmatic trial purpose: which treatment to use

3. Key Differences: Question
Explanatory Can the intervention work?
Pragmatic
Does the intervention work when used in normal practice?

4. Key Differences: Setting
Explanatory
Well resourced
Ideal setting
Pragmatic
Normal practice

5. Key Differences: Participants
Explanatory
Highly selected
Exclude many
poorly adherent patients
those with conditions that might dilute the effect
Homogeneous population
Pragmatic
Little or no selection beyond the clinical indication of interest
Heterogeneous

6. Key Differences: Intervention
Explanatory
Strictly enforced
Adherence is monitored closely
Pragmatic
Applied flexibly as would be in normal practice

7. Key Differences: Outcomes
Explanatory
Often short-term surrogates
Process measurements
Pragmatic
Directly relevant
to participants
to funders
to communities
to healthcare practitioners

8. Key Differences: Relevance to Practice
Explanatory Indirect: little effort made to match the design of the trial to the decision making needs of those in the usual setting in which the intervention will be implemented
Pragmatic
Direct: the trial is designed to meet the needs of those making decisions about treatment options in the setting in which the intervention will be implemented

9. Large Simple Trials: Goals
Idea started in 1980s
Goals
address important health care questions
identify small but worthwhile improvement in major outcomes in common diseases
confirm conclusions from meta-analyses of smaller trials

10. Large Simple Trials: Characteristics
Eligibility based on “uncertainty principle”
Minimal restrictions on care other than assigned treatment
Rigorous attention to control of bias by focusing on control of systematic errors rather than random errors
Reliable assessment of effect of treatment in “real world” setting
Limited data collection

11. Cluster Randomized Trials
Randomization of units instead of individual patients
Examples
randomization of physicians to a particular intervention
randomization of sites to different drug regimens
Design consideration: statistical power depends more on number of clusters than on number of individuals per cluster

12. Divergent Conclusions
Why?
Setting
highly controlled administration; specialized centers (traditional randomized trial)
real practice
Outcomes
biomedical surrogate outcome
measured health gain

13. Key Characteristics of Pragmatic Trials
Focused on questions from and important to stakeholders
Conducted in everyday clinical practice environment (multiple and varied settings) rather than in “parallel research universe”
Intervention tailored to needs of setting, intended for sustained real-world practice, and compared to real world alternatives
Representative populations / few exclusion criteria – enrolled patients are those identified as having greatest need
Multiple outcomes important to decision and policy makers
evaluation based on clinical and administrative data that are highly relevant (e.g., patient reported outcomes already clinically collected, pattern of health service utilization including medication use, and health care costs)

14. Challenges Improve efficiency of patient recruitment
Improve the reliability and validity of clinical information in the EMRs
More actively engage clinicians and implement reward systems that value their participation in pragmatic clinical trials
Decrease regulatory barriers for conducting low- risk pragmatic trials

15. Discussion
Is there a role for pragmatic trials within the older cancer population?