Confidence intervals for the 50 per cent response dose

Area of Science:

• Biostatistics
• Pharmacometrics
• Toxicology

Background:

• Accurate estimation of the 50% response dose is critical in pharmaceutical and toxicological studies.
• Existing methods for confidence intervals, including the Delta method and Fieller's procedure, have limitations.
• Newer methods, such as likelihood ratio-based intervals, are proposed but lack extensive validation.

Purpose of the Study:

• To comprehensively evaluate and compare the performance of various confidence interval methods for the 50% response dose.
• To identify the most reliable and accurate method for constructing these intervals.
• To provide guidance on method selection in dose-response modeling.

Main Methods:

• Extensive simulation study comparing multiple confidence interval calculation methods.
• Evaluation of the Delta method, Fieller's procedure, and likelihood ratio-based intervals.
• Inclusion and assessment of the approximate bootstrap confidence (ABC) procedure and adjusted likelihood ratio intervals.

Main Results:

• The simulation study provides empirical evidence on the coverage and width of different confidence intervals.
• Performance metrics were analyzed across various scenarios to assess method robustness.
• Specific methods demonstrated superior performance in terms of accuracy and precision.

Conclusions:

• The approximate bootstrap confidence (ABC) procedure emerged as a highly recommended method for calculating confidence intervals for the 50% response dose.
• Adjusted likelihood ratio-based intervals also showed promise, offering competitive performance.
• The findings suggest a shift towards more robust methods in dose-response analysis.