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arXiv · 2507.11861

Bias reduction method for prior event rate ratio, with application to emergency department visit rates in patients with advanced cancer

Xiangmei Ma·Chetna Malhotra·Eric Andrew Finkelstein·Yin Bun Cheung
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Abstract

Objectives: Prior event rate ratio (PERR) is a promising approach to control confounding in observational and real-world evidence research. One of its assumptions is that occurrence of outcome events does not influence later event rate, or in other words, absence of 'event dependence'. This study proposes, evaluates and illustrates a bias reduction method when this assumption is violated. Study Design and Setting: We propose the conditional frailty method for implementation of PERR in the presence of event dependence and evaluate its performance by simulation. We demonstrate the use of the method with a study of emergency department visit rate and palliative care in patients with advanced cancer in Singapore. Results: Simulations showed that, in the presence of negative (positive) event dependence, the crude PERR estimate of treatment effect was biased towards (away from) the null value. The proposed method successfully reduced the bias, with median of absolute level of relative bias at about 5%. Dynamic random-intercept modelling revealed positive event dependence in emergency department visits among patients with advanced cancer. While conventional time-to-event regression analysis with covariate adjustment estimated higher rate of emergency department visits among palliative care recipients (HR=3.61, P<0.001), crude PERR estimate and the proposed PERR estimate were 1.45 (P=0.22) and 1.22 (P=0.57), respectively. Conclusions: The proposed bias reduction method mitigates the impact of violation of the PERR assumption of absence of event dependence. It allows broader application of the PERR approach.

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Xiangmei Ma, Chetna Malhotra, Eric Andrew Finkelstein, Yin Bun Cheung. 2025-07-16. Bias reduction method for prior event rate ratio, with application to emergency department visit rates in patients with advanced cancer. https://arxiv.org/abs/2507.11861

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