A New Source of Heterogeneity in Comparative and Translational Clinical Trials: The "Border-Time" Bias
Mariachiara Santorsola1, Michele Caraglia2, Guglielmo Nasti1
1Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale", Via M. Semmola, 80131 Naples, Italy.
Abstract:
The use of target-oriented drugs is profoundly changing the anti-cancer treatments. This new and expanding therapeutic context relies on the translation of biomarkers expression (laboratory testing) into clinical practice (treatment). Progression-free survival is a primary or co-primary endpoint in the large part of comparative clinical trials about biologic anti-cancer agents. Here, we describe the "border time" bias represented by specific time points and intervals that are an underestimated source of methodologic heterogeneity and can contribute to wrong evaluation of time-to-outcome. These issues are concentrated at the beginning (head: pre-screening and screening activities) and at the end (tail: modalities of disease reassessment) of the anti-cancer treatment and can represent a time-related bias. Reporting, and ideally shortening, the time spent in pre-screening and screening activities with synthetic and innovative methodological tools as well as more harmonized rules about timing of disease reassessment can contribute to reduce, or even prevent, this bias in clinical studies.
Insights
Targeted cancer therapies rely on biomarker expression. This study identifies "border time" bias in clinical trials, affecting progression-free survival evaluation due to screening and reassessment timing issues.
Area of Science:
- Oncology
- Clinical Trial Methodology
- Biomarker Research
Background:
- Targeted anti-cancer drugs are revolutionizing cancer treatment by integrating biomarker expression from laboratory testing into clinical practice.
- Progression-free survival is a key endpoint in clinical trials for biologic anti-cancer agents, necessitating accurate time-to-outcome evaluation.
Purpose of the Study:
- To describe the "border time" bias, an underestimated source of methodological heterogeneity in anti-cancer clinical trials.
- To highlight how specific time points and intervals, particularly during screening and disease reassessment, can lead to inaccurate evaluations of time-to-outcome.
Main Methods:
- Analysis of time-related factors in anti-cancer treatment protocols.
- Identification of bias sources at the beginning (pre-screening and screening) and end (disease reassessment) of treatment phases.
Main Results:
- "Border time" bias arises from specific time points and intervals in clinical trials.
- This bias is concentrated in pre-screening, screening activities, and disease reassessment modalities.
- These factors can lead to a wrong evaluation of time-to-outcome, impacting progression-free survival assessment.
Conclusions:
- Reducing "border time" bias is crucial for accurate clinical trial results in targeted cancer therapy.
- Shortening pre-screening and screening times using innovative tools and harmonizing disease reassessment rules can mitigate this bias.
- Addressing these methodological issues will improve the reliability of clinical studies evaluating anti-cancer agents.
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