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Stat Med. 2018 Jun 30;37(14):2187-2207. doi: 10.1002/sim.7685. Epub 2018 Apr 17.

Predictive probability methods for interim monitoring in clinical trials with longitudinal outcomes.

Author information

1
Global Biometric Sciences, Bristol-Myers Squibb, New Jersey, United States.
2
Translational Informatics, Sanofi, Bridgewater, New Jersey, United States.

Abstract

In clinical research and development, interim monitoring is critical for better decision-making and minimizing the risk of exposing patients to possible ineffective therapies. For interim futility or efficacy monitoring, predictive probability methods are widely adopted in practice. Those methods have been well studied for univariate variables. However, for longitudinal studies, predictive probability methods using univariate information from only completers may not be most efficient, and data from on-going subjects can be utilized to improve efficiency. On the other hand, leveraging information from on-going subjects could allow an interim analysis to be potentially conducted once a sufficient number of subjects reach an earlier time point. For longitudinal outcomes, we derive closed-form formulas for predictive probabilities, including Bayesian predictive probability, predictive power, and conditional power and also give closed-form solutions for predictive probability of success in a future trial and the predictive probability of success of the best dose. When predictive probabilities are used for interim monitoring, we study their distributions and discuss their analytical cutoff values or stopping boundaries that have desired operating characteristics. We show that predictive probabilities utilizing all longitudinal information are more efficient for interim monitoring than that using information from completers only. To illustrate their practical application for longitudinal data, we analyze 2 real data examples from clinical trials.

KEYWORDS:

conditional power; interim monitoring; longitudinal data; predictive probability

PMID:
29664214
DOI:
10.1002/sim.7685

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