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Bias Control in Randomized Controlled Clinical Trials

  • Diane Uschner
  • William F. RosenbergerEmail author
Living reference work entry

Abstract

In clinical trials, randomization is used to allocate patients to treatment groups, because this design technique tends to produce comparability across treatment groups. However, even randomized clinical trials are still susceptible to bias. Bias is a systematic distortion of the treatment effect estimate. This chapter introduces two types of bias that may occur in clinical trials, selection bias and chronological bias. Selection bias may arise from predictability of the randomization sequence, and different models for predictability are presented. Chronological bias occurs due to unobserved time trends that influence patients’ responses, and its effect on the rejection rate of parametric hypothesis tests for the treatment effect will be revealed. It will be seen that different randomization procedures differ in their susceptibility to bias. A method to reduce bias at the design stage of the trial and robust testing strategies to adjust for bias at the analysis stage are presented to help to mitigate the potential for bias in randomized controlled clinical trials.

Keywords

Selection bias Chronological bias Restricted randomization Type I error Power 

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of StatisticsGeorge Mason UniversityFairfaxUSA
  2. 2.Biostatistics CenterThe George Washington UniversityRockvilleUSA

Section editors and affiliations

  • O. Dale Williams
    • 1
  1. 1.Department of MedicineUniversity of AlabamaBirminghamUSA

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