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NIH Collaboratory
Living Textbook of
Pragmatic Clinical Trials

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Rethinking Clinical Trials

A Living Textbook of Pragmatic Clinical Trials

  • Design
    • What is a Pragmatic Clinical Trial?
    • Decentralized Pragmatic Clinical Trials
    • Developing a Compelling Grant Application
    • Experimental Designs and Randomization Schemes
    • Endpoints and Outcomes
    • Analysis Plan
    • Using Electronic Health Record Data
    • Building Partnerships and Teams to Ensure a Successful Trial
    • Intervention Delivery and Complexity
    • Patient Engagement
  • Data, Tools & Conduct
    • Assessing Feasibility
    • Acquiring Real-World Data
    • Assessing Fitness-for-Use of Real-World Data
    • Study Startup
    • Participant Recruitment
    • Monitoring Intervention Fidelity and Adaptations
    • Patient-Reported Outcomes
    • Clinical Decision Support
    • Mobile Health
    • Electronic Health Records–Based Phenotyping
    • Navigating the Unknown
  • Dissemination & Implementation
    • Data Sharing and Embedded Research
    • Dissemination Approaches for Different Audiences
    • Implementation
    • End-of-Trial Decision-Making
  • Ethics & Regulatory
    • Privacy Considerations
    • Identifying Those Engaged in Research
    • Collateral Findings
    • Consent, Disclosure, and Non-Disclosure
    • Data and Safety Monitoring
    • Ethical Considerations of Data Sharing in Pragmatic Clinical Trials
    • Ethics for AI and ML
    • IRB Responsibilities and Procedures

Unequal Cluster Sizes

CHAPTER SECTIONS

Analysis Plan


Section 3

Unequal Cluster Sizes

Expand Contributors

Patrick J. Heagerty, PhD
Elizabeth R. DeLong, PhD
For the NIH Pragmatic Trials Collaboratory Biostatistics and Study Design Core

Contributing Editors
Damon M. Seils, MA
Jonathan McCall, MS

One challenge that may arise with cluster randomization is that, although a cluster’s units are typically assumed to be of equivalent size, this may not be true of cluster randomized trials in healthcare settings. Clusters such as physician practices or clinics may be of substantially different sizes, which can affect the statistical power of the study and decisions about sample size (Cook et al 2016). To address these issues, study statisticians need an estimate of the range in potential sample sizes. For example, in a trial that randomly assigns clinics to an intervention that will be applied to patients who are newly diagnosed with diabetes, the statistician will need information about the number of such patients coming into each clinic over the past several months. The statistician will then consider the range in sample sizes when calculating the number of clinics and patients needed for the study.

Previous Section Next Section

SECTIONS

CHAPTER SECTIONS

sections

  1. Introduction
  2. Intraclass Correlation
  3. Unequal Cluster Sizes
  4. Accounting for Residual Confounding in the Analysis
  5. Missing Data and Intention-to-Treat Analyses
  6. Electronic Health Record Data Extraction
  7. Unanticipated Changes
  8. Interim Reassessment of Sample Size in Cluster Randomized Trials
  9. Case Study: STOP CRC Trial

Resources

Unequal Cluster Sizes in Cluster-Randomized Clinical Trials
A guidance document from the Biostatistics and Study Design Core

REFERENCES

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Cook AJ, Delong E, Murray DM, Vollmer WM, Heagerty PJ. 2016. Statistical lessons learned for designing cluster randomized pragmatic clinical trials from the NIH Health Care Systems Collaboratory Biostatistics and Design Core. Clin Trials. 13:504-512. doi:10.1177/1740774516646578. PMID: 27179253.

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Version History

June 23, 2022: Updated the name of the NIH Collaboratory in the contributors list and made nonsubstantive changes to the text as part of the annual content update (changes made by D. Seils).

July 2, 2020: Minor corrections to layout and formatting (changes made by D. Seils).

May 27, 2020: Added Heagerty to the contributors list and reordered the sections of this chapter as part the annual content update (changed made by D. Seils).

May 1, 2020: Made nonsubstantive formatting changes to the text as part of the annual content update (changes made by D. Seils).

January 16, 2019: Made nonsubstantive changes to the text as part of the annual content update (changes made by D. Seils).

Published August 25, 2017

current section :

Unequal Cluster Sizes

  1. Introduction
  2. Intraclass Correlation
  3. Unequal Cluster Sizes
  4. Accounting for Residual Confounding in the Analysis
  5. Missing Data and Intention-to-Treat Analyses
  6. Electronic Health Record Data Extraction
  7. Unanticipated Changes
  8. Interim Reassessment of Sample Size in Cluster Randomized Trials
  9. Case Study: STOP CRC Trial

Citation:

Heagerty PJ, DeLong ER; for the NIH Health Care Systems Research Collaboratory Biostatistics and Study Design Core. Analysis Plan: Unequal Cluster Sizes. In: Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials. Bethesda, MD: NIH Pragmatic Trials Collaboratory. Available at: https://rethinkingclinicaltrials.org/chapters/design/analysis-plan-top/unequal-cluster-sizes/. Updated June 23, 2022. DOI: 10.28929/017.

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