Studying When to Add Biological Therapy to Cytotoxic Therapy in Advanced Cancer Care Using Real World Data: How to...

Area of Science:

• Oncology
• Clinical Trial Design
• Biostatistics

Background:

• Real-world data often lack treatment assignment details, potentially leading to immortal time bias.
• Selection bias and treatment strategy misclassification can occur in advanced cancer studies.
• Immortal time bias can distort survival estimates in observational studies.

Purpose of the Study:

• To identify design choices that introduce immortal time bias in observational studies.
• To propose unbiased alternative methods for analyzing real-world data.
• To evaluate monoclonal antibody (mAb) sequencing strategies in colorectal cancer (CRC) for overall survival.

Main Methods:

• A target trial was specified to compare early vs. late mAb initiation in CRC.
• Eligibility criteria were aligned with first-line chemotherapy initiation to avoid bias.
• Methods like cloning, censoring, weighting, and sequential emulation were used to address immortal time bias.

Main Results:

• Unbiased analyses showed no significant survival difference between mAb sequencing strategies.
• Biased analyses, introducing immortal time, suggested an early survival benefit for later mAb initiation.
• CCW and sequential emulation yielded comparable, non-significant survival estimates.

Conclusions:

• Monoclonal antibody sequencing strategies do not appear to impact overall survival in CRC.
• Misalignment of time zero, treatment assignment, and eligibility criteria can introduce immortal time bias.
• Robust study designs are essential for accurate real-world evidence generation.