Matching in Organ Impairment Studies: A Systematic Review of Accepted Methodologies

Abstract

Although the use of demographic matching in organ impairment studies is recommended to exclude the confounding effect of demographics on the pharmacokinetic (PK) study results, very little guidance exists on the practical implementation of this approach. Individual matching (IM) as well as several strategies for group matching (GM) have been described in literature. We conducted a systematic review, including 170 renal (RI) and 173 hepatic impairment (HI) studies completed in the last 25 years and characterized used matching methodologies and selected matching criteria. In RI, GM appears more common (70%), while in HI IM was preferred (55%). Age, body weight or body mass index (BMI), and sex were the most commonly used matching criteria, with the most common acceptance margins of ± 10 years for age, ± 10-20% for body weight, and ± 15-20% for BMI, irrespective of matching method used. While IM required notably more subjects in the control group, we did not find a significant effect of various matching strategies on study duration or recruitment between different matching strategies. No matching was used in most of the studies conducted in the target patient population with organ impairment, as opposed to the studies conducted in general organ impairment population without the target indication. Based on the results of this review, we proposed a framework for selection of matching strategy, with IM being a recommended matching method in most cases and GM being suitable for compounds that have well-characterized impact of demographic characteristics on PK and a low between-subject variability.

Keywords: Clinical trials; Hepatic impairment; Organ impairment; Renal impairment.