Biostatistics and Study Design
Overview
Co-chairs:
Core goal: Develop guidance regarding study design and biostatistical issues relevant to pragmatic clinical trials.
Pragmatic clinical trials present biostatistical and study design issues in addition to those typically encountered in traditional clinical trials. For example, when randomizing clusters rather than individuals, issues include:
- Trade-off between sample size and potential contamination
- Intraclass correlation at different levels
- Varying cluster sizes
- Need for stratification or matching
In addition, special consideration must be given to handling informative missing follow-up data when using electronic health records as the basis for follow-up data collection. Ignoring the missing data issue could lead to biased results, including concluding that an effective intervention is not effective.
Tools for Data and Safety Monitoring
- Data Monitoring in Pragmatic Clinical Trials: Points to Consider
- Charter Template for Data Monitoring Committees of Pragmatic Clinical Trials
- Data and Safety Monitoring Living Textbook Chapter
- Data Monitoring Committees for Pragmatic Clinical Trials
- Principles and Procedures for Data and Safety Monitoring in Pragmatic Clinical Trials
- Additional Resources
Areas of Focus
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Work with the NIH Collaboratory Trial teams to address gaps and limitations in their statistical plans and study designs during the planning phase.
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Understand which methods can be directly applied in a distributed data setting, which can potentially be modified for the distributed data setting, and which will require individual-level data.
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Document new statistical and methodological issues that arise and share knowledge through these case studies.
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Gather input on key methodological issues from NIH collaborators, investigators, and academic institutions.
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Identify areas in need of methods development and work to address these methodology challenges.
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Generate new knowledge by studying the application of statistical techniques (eg, constrained randomization) in pragmatic and cluster randomized trial designs.
Interview
During the NIH Pragmatic Trials Collaboratory 2024 Steering Committee meeting, Drs. Liz Turner and Patrick Heagerty discussed study design challenges and lessons learned in their work as cochairs of the Biostatistics and Study Design Core.
News and Interviews
- News_New Podcast Calls Attention to Underrecognized IRGT Trial Design
March 26, 2026: New Podcast Calls Attention to Underrecognized IRGT Trial Design
- News_A Year of Trial Results and Innovations From the NIH Pragmatic Trials Collaboratory
December 15, 2025: A Year of Trial Results and Innovations From the NIH Pragmatic Trials Collaboratory
- News_P Values vs Decision-Maker Perspectives, in a Special Grand Rounds Session on September 26
September 8, 2025: P Values vs Decision-Maker Perspectives, in a Special Grand Rounds Session on September 26
- News_A Year of Innovations and Insights From the NIH Pragmatic Trials Collaboratory
December 12, 2024: A Year of Innovations and Insights From the NIH Pragmatic Trials Collaboratory
- News_Case Study Describes a Reassessment of Sample Size in an Ongoing Cluster Randomized Trial
October 15, 2024: Case Study Describes a Reassessment of Sample Size in an Ongoing Cluster Randomized Trial
- News_NIH Collaboratory Biostatisticians Evaluate Analytic Models for Individually Randomized Group Treatment Trials
September 12, 2024: NIH Collaboratory Biostatisticians Evaluate Analytic Models for Individually Randomized Group Treatment Trials
- News_Ethics Core and Biostatistics Core Guide Newest Trials Through Planning Phase
August 19, 2024: Ethics Core and Biostatistics Core Guide Newest Trials Through Planning Phase
- News_Special Biostatistics Series Concludes With Missing Data in Cluster Randomized Trials
January 3, 2024: Special Biostatistics Series Concludes With Missing Data in Cluster Randomized Trials
- News_A Year of New Insights From the NIH Pragmatic Trials Collaboratory
December 12, 2023: A Year of New Insights From the NIH Pragmatic Trials Collaboratory
- News_Special Biostatistics Series Continues With Guidelines for Stepped-Wedge Trials
November 29, 2023: Special Biostatistics Series Continues With Guidelines for Stepped-Wedge Trials
Products and Publications
- Curtis et al Contemp Clin Trials 2025
Monitoring in pragmatic trials lessons from the NIH Pragmatic Trials Collaboratory
- Moyer et al Stat Med 2024
Evaluating analytic models for individually randomized group treatment trials with complex clustering in nested and crossed designs
- Li et al Stat Med 2024
Planning stepped wedge cluster randomized trials to detect treatment effect heterogeneity
- Voldal et al Stat Med 2024
Robust analysis of stepped wedge trials using composite likelihood models
- Wang et al Stat Med 2024
Designing individually randomized group treatment trials with repeated outcome measurements using generalized estimating equations
- Wang et al Biom J 2023
Improving sandwich variance estimation for marginal Cox analysis of cluster randomized trials
- Moyer et al Trials 2022
Analysis of multiple-period group randomized trials: random coefficients model or repeated measures ANOVA?
- Li et al Biostatistics 2022
Designing three-level cluster randomized trials to assess treatment effect heterogeneity
- Wang et al Contemp Clin Trials 2022
Two weights make a wrong: cluster randomized trials with variable cluster sizes and heterogeneous treatment effects
- Federico et al Contemp Clin Trials 2022
Ethical and epistemic issues in the design and conduct of pragmatic stepped-wedge cluster randomized clinical trials
Presentations
- Biostats and Study Design Slides OCT2025
Onboarding Meeting October 29 - Biostatistics and Study Design Intro
- Biostats and Study Design Slides 28OCT2025
Onboarding Meeting October 28 - Biostatistics and Study Design Intro
- GR-Video-09-26-25
Significance in ePCTs: P Values vs Decision-Maker Perspectives
- GR-Slides-09-26-25
Significance in ePCTs: P Values vs Decision-Maker Perspectives
- 00_Simon_P Values_Approved_combined_DONE
Significance in ePCTs: P Values vs Decision-Maker Perspectives
- Biostats Core Slides JAN2025
Onboarding Meeting Jan 2025 - Biostatistics and Study Design Intro
- Biostats Core Slides NOV2024
Onboarding Meeting Nov 2024 - Biostatistics and Study Design Intro
- Biostats_Core Onboarding Slides_18OCT2024_Final
Onboarding Meeting October 2024 - Biostatistics and Study Design Intro
- GR-Video-01-05-24
Methods for Handling Missing Data in Cluster Randomized Trials (GR Video 2024)
- GR-Slides-01-05-24
Methods for Handling Missing Data in Cluster Randomized Trials (GR Slides 2024)