Statistics in Biosciences

, Volume 5, Issue 2, pp 344–360 | Cite as

An Analytic Framework for Aligning Observational and Randomized Trial Data: Application to Postmenopausal Hormone Therapy and Coronary Heart Disease

  • Sengwee TohEmail author
  • Joann E. Manson


We describe a conceptual analytic framework for aligning observational and randomized controlled trial (RCT) data. The framework allows one to (1) use observational data to estimate treatment effects comparable to their RCT counterparts, (2) properly include early events that occur soon after treatment initiation in the analysis of observational data, (3) estimate various treatment effects that are of clinical and scientific relevance while appropriately adjusting for time-varying confounders in both the RCT and observational analyses, (4) assess the generalizability of RCT findings in the more diverse populations generally found in the observational data, and (5) combine both types of data to study associations that cannot be addressed by one study or a single data set. We describe the theoretical application of this framework to the Women’s Health Initiative data to examine the relation between postmenopausal hormone therapy and coronary heart disease. The analytic framework can be tailored to specific exposure-outcome associations and data sources, and may be refined as more is learned about its strengths and limitations.


Postmenopausal hormone therapy Coronary heart disease Marginal structural model Comparative effectiveness research Pharmacoepidemiology Pragmatic trials 



Dr. Toh is partially supported by the Agency for Healthcare and Research Quality (R03HS019024). Dr. Manson is partially supported by the National Heart, Lung, and Blood Institute (R01HL034594, R01HL088521, and N0I-WH32109).


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Copyright information

© International Chinese Statistical Association 2012

Authors and Affiliations

  1. 1.Department of Population MedicineHarvard Medical School and Harvard Pilgrim Health Care InstituteBostonUSA
  2. 2.Division of Preventive Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

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