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Related Experiment Video

Updated: Jun 24, 2026

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition

Published on: September 20, 2019

Sequential designs for ordinal phase I clinical trials.

Guohui Liu¹, William F Rosenberger, Linda M Haines

¹Department of Biostatistics, Millennium Pharmaceuticals, Inc. 40 Landsdowne Street, Cambridge, MA 02139, USA. Guohui.liu@mpi.com

Biometrical Journal. Biometrische Zeitschrift

|April 10, 2009

Summary

This study addresses challenges in early-phase clinical trial designs using maximum likelihood estimates (MLE). A novel sequential approach is proposed to improve dose-finding for small trials with ordinal responses.

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Last Updated: Jun 24, 2026

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition

Published on: September 20, 2019

Area of Science:

Clinical Trials
Biostatistics
Pharmacometrics

Background:

Sequential designs in early-phase clinical trials face estimation challenges due to limited early data.
Maximum Likelihood Estimation (MLE) can be problematic in small trials, particularly with ordinal responses.
The nonexistence of MLE for logistic parameters under proportional odds models is a specific issue.

Purpose of the Study:

To develop a robust sequential design for small phase I clinical trials with ordinal responses.
To address the nonexistence of MLE in logistic regression models within sequential trial designs.
To propose an optimal sequential approach integrating ethical considerations and MLE probability.

Main Methods:

Developed a sequential optimal approach comprising start-up, follow-on, and dose-finding designs.
Incorporated the probability of an undetermined MLE as a design restriction.
Utilized simulation studies with parameters from a real dataset for comparisons.

Main Results:

The proposed sequential optimal approach aims to overcome MLE limitations in early-phase trials.
The design incorporates ethical considerations and addresses potential estimation issues.
Simulation studies provide performance comparisons with nonparametric sequential designs.

Conclusions:

The novel sequential design offers a more reliable method for dose-finding in small phase I trials.
This approach enhances the estimation process by managing MLE nonexistence and ethical factors.
The study contributes to the advancement of adaptive clinical trial methodologies.