TY - JOUR

T1 - Semi-blinded design in clinical trials

AU - Wan, Shu Mei

AU - Balakrishnan, Narayanaswamy

AU - Manurung, Monica Mayeni

AU - Chang, Kwang Hwa

AU - Wu, Chien Hua

N1 - Publisher Copyright:
© 2022 Taylor & Francis Group, LLC.

PY - 2023

Y1 - 2023

N2 - The semi-blinded design can be applied for the adaptive design in clinical trials. According the the FDA guidance, an adaptive clinical design study would modify the study design and hypotheses based on the analysis of accrued data. An independent Data Monitoring Committee analyzes the unblinded data in the middle of a clinical trial and makes recommendations to the sponsor if any action is needed. The unblinded interim analysis could potentially introduce bias and put the integrity of the trial at risk. The proposed methodology is technically blinded for the interim analysis. In fact, actual treatment labels are not released. It is based on a treatment re-labeling approach in which the dummy treatments associated with the actual treatments via a pre-specified transition probability matrix are released in the dataset. The semi-blinded test statistic depends on this transition probability matrix. However, it can be evaluated without knowing the transition probability matrix if this matrix is a Latin square. As the stagnation probability approach to 0.5, the more information we will lose. It will lead to obtain a lower power of testing hypothesis, and may not be able to show the utility or efficacy of study treatment if this probability is close to 0.5. The higher the stagnation probability, the higher disclosure risk we have. The randomization codes may be broken as the stagnation probability approach to 1. The sponsor should strike a balance between the statistical power and disclosure risk.

AB - The semi-blinded design can be applied for the adaptive design in clinical trials. According the the FDA guidance, an adaptive clinical design study would modify the study design and hypotheses based on the analysis of accrued data. An independent Data Monitoring Committee analyzes the unblinded data in the middle of a clinical trial and makes recommendations to the sponsor if any action is needed. The unblinded interim analysis could potentially introduce bias and put the integrity of the trial at risk. The proposed methodology is technically blinded for the interim analysis. In fact, actual treatment labels are not released. It is based on a treatment re-labeling approach in which the dummy treatments associated with the actual treatments via a pre-specified transition probability matrix are released in the dataset. The semi-blinded test statistic depends on this transition probability matrix. However, it can be evaluated without knowing the transition probability matrix if this matrix is a Latin square. As the stagnation probability approach to 0.5, the more information we will lose. It will lead to obtain a lower power of testing hypothesis, and may not be able to show the utility or efficacy of study treatment if this probability is close to 0.5. The higher the stagnation probability, the higher disclosure risk we have. The randomization codes may be broken as the stagnation probability approach to 1. The sponsor should strike a balance between the statistical power and disclosure risk.

KW - adaptive design

KW - ANOVA model

KW - Semi-blinded design

KW - transition probability matrix

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U2 - 10.1080/03610926.2022.2042024

DO - 10.1080/03610926.2022.2042024

M3 - Article

AN - SCOPUS:85126049296

SN - 0361-0926

VL - 52

SP - 7165

EP - 7183

JO - Communications in Statistics - Theory and Methods

JF - Communications in Statistics - Theory and Methods

IS - 20

ER -