A pragmatic dose-finding approach using short-term surrogate efficacy outcomes to evaluate binary efficacy and...

Area of Science:

• Clinical Trials
• Oncology
• Biostatistics

Background:

• Phase I/II cancer trials require simultaneous evaluation of efficacy and toxicity.
• Current dose-finding methods often rely on binary outcomes (e.g., dose-limiting toxicity, objective response) with differing timeframes.
• The delayed confirmation of objective responses significantly prolongs study duration.

Purpose of the Study:

• To propose a novel dose-finding approach for cancer clinical trials that addresses the issue of prolonged study duration.
• To utilize unconfirmed early responses as a surrogate for confirmed efficacy outcomes.
• To reduce irrelevant dose selection and bias while accelerating study completion.

Main Methods:

• Proposed an approach using unconfirmed early responses as a surrogate for confirmed efficacy outcomes.
• Incorporated a mechanism to replace surrogate outcomes with confirmed outcomes when available.
• Developed modified likelihood functions and outcome variable definitions for implementation.
• Conducted simulation studies to evaluate the approach's utility.

Main Results:

• The proposed approach demonstrated positive utility in simulation studies.
• The method is expected to significantly shorten study duration.
• It can reduce irrelevant dose selection and accumulation of bias.
• Three variations of the approach were developed and shown to be easily implementable.

Conclusions:

• The novel approach effectively uses surrogate efficacy outcomes to shorten phase I/II cancer trial durations.
• This method offers a practical solution to a significant barrier in implementing advanced dose-finding strategies.
• The approach facilitates more efficient simultaneous evaluation of efficacy and toxicity in early-phase oncology studies.