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.
Presentation
Dr. Andrea Cook of the University of Washington and the Group Health Research Institute discusses biostatistical and study design challenges in pragmatic clinical trials.
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.
News & Interviews
- 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
- News_Special Biostatistics Series Continues With Complex Clustering in Pragmatic Trials
November 1, 2023: Special Biostatistics Series Continues With Complex Clustering in Pragmatic Trials
- News_NIH Pragmatic Trials Collaboratory Announces Grand Rounds Series
September 5, 2023: NIH Pragmatic Trials Collaboratory Announces Grand Rounds Series on Design and Analysis of Pragmatic Clinical Trials
- News_Li Receives New PCORI Award
April 10, 2023: Li Receives New PCORI Award to Develop Causal Inference Methods for Stepped-Wedge Cluster Randomized Trials
- News_Biostatistics Core Sponsors This Week’s PCT Grand Rounds
March 8, 2023: Biostatistics Core Sponsors This Week’s PCT Grand Rounds on Estimands in Cluster Randomized Trials
- News_IMPACT Grand Rounds on Treatment Effect Heterogeneity in Cluster Randomized Trials
February 14, 2023: IMPACT Collaboratory to Host Grand Rounds on Treatment Effect Heterogeneity in Cluster Randomized Trials
- News_Wealth of New Insights From the NIH Pragmatic Trials Collaboratory
December 13, 2022: In Our Tenth Year, a Wealth of New Insights From the NIH Pragmatic Trials Collaboratory
- News_Biostatistics Core Develops Tools and Strategies for Common Research Challenges
August 16, 2022: Biostatistics Core Develops Tools and Strategies for Common Research Challenges
Products and Publications
- 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
- COVID-19 SAP Checklist
Statistical Analysis Plan Checklist for Addressing COVID-19 Impacts
- Li et al Stat Methods Med Res 2020
Mixed-effects models for the design and analysis of stepped wedge cluster randomized trials: an overview
- Design Analysis of Embedded Pragmatic Clinical Trials Workshop Summary
Design and Analysis of Embedded Pragmatic Clinical Trials Workshop Summary
- Intraclass_Correlation_Coefficient_Cheat_Sheet_March_15_2020
Intraclass Correlation Coefficient Cheat Sheet
- Missing-Data-ITT_V1.02
Analyses of Randomized Controlled Trials in the Presence of Noncompliance and Study Dropout
- Li F et al Stat Med 2017
An evaluation of constrained randomization for the design and analysis of group-randomized trials with binary outcomes
- Living Textbook Chapter_Analysis Plan
Living Textbook Chapter: Analysis Plan
- Living Textbook Chapter_Experimental Designs and Randomization Schemes
Living Textbook Chapter: Experimental Designs and Randomization Schemes
- Cook et al Clin Trials 2016
Statistical lessons learned for designing cluster randomized pragmatic clinical trials from the NIH Health Care Systems Collaboratory Biostatistics and Design Core
- Li F et al Stat Med 2016
An evaluation of constrained randomization for the design and analysis of group-randomized trials
- Variance-correction-for-GEE_V1.R0
Small-Sample Robust Variance Correction for Generalized Estimating Equations for Use in Cluster Randomized Clinical Trials
- Biostats_frailty_guidance
Frailty Models in Cluster-Randomized Trials
- Intraclass-correlation-coeffecient_V1.0
The Intraclass Correlation Coefficient (ICC)
- Extracting-EHR-data_V1.0
Key Issues in Extracting Usable Data from Electronic Health Records for Pragmatic Clinical Trials
- Varying-cluster-sizes_V1.0
Unequal Cluster Sizes in Cluster-Randomized Clinical Trials
- Pairing-vs-stratification_V1.0
Pair-Matching vs Stratification in Cluster-Randomized Trials
Presentations
- 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)
- GR-Video-12-01-23
Guidelines for Design and Analysis of Stepped-Wedge Trials (GR Video 2023)
- GR-Slides-12-01-23
Guidelines for Design and Analysis of Stepped-Wedge Trials (GR Slides 2023)
- GR-Video-11-03-23
The Perils and Pitfalls of Complex Clustering in Pragmatic Trials (GR Video 2023)
- GR-Slides-11-03-23
The Perils and Pitfalls of Complex Clustering in Pragmatic Trials (GR Slides 2023)
- GR-Video-10-06-23
Hybrid Studies Should Not Sacrifice Rigorous Methods (GR Video 2023)
- GR-Slides-10-06-23
Hybrid Studies Should Not Sacrifice Rigorous Methods (GR Slides 2023)
- 2023-Biostatistics-Grand-Rounds-Series-Flyer
Advances in the Design and Analysis of Pragmatic Clinical Trials
- 2023 AcademyHealth Workshop_Day 1_Heagerty_Design + Analysis
ePCT Experimental Design and Analysis
- Cluster Trials_Special Interest Group_Meeting_Wang Webinar
Improving sandwich variance estimation for marginal Cox analysis of cluster randomized trials
- 2022 NIH Workshop_Heagerty
2022 NIH Workshop Panel 2 Moderator Slides
- SC-Mtg-2022-Day-1-Heagerty
Dr. Patrick Heagerty's Presentation at 2022 Steering Committee Meeting
- Turner_Collaboratory_SC_14APR2021
Steering Committee Meeting (Virtual 2021) COVID-19 Effects on Study Design & Analysis
- Presentation_Biostats_NIHODP_2020_c
Overview of Statistical Models for the Design and Analysis of Stepped Wedge Cluster Randomized Trials (NIH Seminar 2020)
- GR-Video-06-19-20
Living Textbook Grand Rounds Series: Part 4-Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials (GR Video 2020)
- GR-Slides-06-19-20
Living Textbook Grand Rounds Series: Part 4-Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials (GR Slides 2020)
- Workshop on the Design and Analysis of Pragmatic Clinical Trials
Workshop on the Design and Analysis of Pragmatic Clinical Trials
- Presentataion_Biostats_CTSA_2018_c
Biostats Core Lessons Learned Presentation (CTSA Forum 2018)
- 6.-DeLong_Biostatistics_FINAL
Biostatistics and Study Design Core - Lessons Learned
- Topic 4-Design+Analysis
ePCT Workshop Topic 4-Design and Analysis
- GR-Slides-2-9-18
Linking Design to Analysis of Cluster Randomized Trials: Covariate Balancing Strategies (GR Slides 2018)
- GR-Video-02-09-18
Linking Design to Analysis of Cluster Randomized Trials: Covariate Balancing Strategies (GR Video 2018)
- GR-Slides-12-02-16
Lessons Learned from the NIH Collaboratory Biostatistics and Design Core (GR Slides 2016)
- GR-Video-12-02-16
Lessons Learned from the NIH Collaboratory Biostatistics and Design Core (GR Video 2016)
- Delong_2016-05-06 2 Control Group Slides
Unstable Control Groups in Pragmatic Trials
- GR-Video-06-19-15
Improving Pragmatic Clinical Trials: Lessons Learned from the NIH Collaboratory Biostatistics Core (GR Video 2015)
- GR-Slides-06-19-15
Improving Pragmatic Clinical Trials: Lessons Learned from the NIH Collaboratory Biostatistics Core (GR Slides 2015)
- DeLong_Collaboratory meeting August 19 2014
Biostatistics Core Update at 2014 SC Meeting
- NIH-Collaboratory-Biostatistics_Lokhnygina_2-25-2014
Biostatistics and Study Design Working Group Report