Hidden Baseline Heterogeneity Can Mask Treatment Effects in Randomized Xenograft Studies: A Scientific Reports Paper Shows Baseline-Aware Analysis Revealing a Responder Subpopulation Pooled Analysis Missed
A paper published in Scientific Reports on November 7 by Gül and Hekim, titled "Hidden baseline heterogeneity can mask treatment effects in randomized xenograft studies," argues that randomization and standardized analytical workflows, while central to preclinical oncology, do not necessarily ensure biological comparability at baseline. The authors test this using a real-world xenograft efficacy dataset generated under standard contract research organization (CRO) conditions.
Although treatment groups appeared balanced at study entry by conventional summaries, baseline tumour volume exhibited latent structure within the cohort. Pooled group-level analyses reported no significant treatment effect, whereas baseline-aware evaluation of tumour growth trajectories revealed a responder subpopulation whose signal had been masked by aggregation. The authors also observed that baseline tumour volume heterogeneity is common under routine preclinical workflows and can similarly alter efficacy interpretation.
They conclude that baseline tumour burden is a biologically consequential source of hidden heterogeneity, and that baseline-aware analytical strategies can improve the sensitivity and interpretability of preclinical efficacy assessment without deviation from standard experimental practice. The work was conducted within the XJENZA Malta-supported program of the Foundation for Cancer Research and Innovation Hub Malta (CRIHM), under grant reference CRP-2024-11. The paper is formally published and peer-reviewed; its findings rest on re-analysis of the real-world dataset rather than new animal experiments.
(Source: Scientific)
Source: Scientific
Published by GSM · USA (original Chinese edition)
Photo: 图：肿瘤组织显微图像（资料图）。CC BY-SA 3.0，经 Wikimedia Commons。 / Photo: Microscopic image of tumour tissue (file photo). CC BY-SA 3.0, via Wikimedia Commons.
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