A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney function

Abstract

Reduced kidney function (or kidney dysfunction) is commonly an exclusion criterion for randomised controlled trials (RCTs) in cancer. Consequently, high quality evidence for anticancer drug dosing in reduced kidney function is limited and no internationally agreed guidelines exist to inform prescribing decisions in this population. A methodology for guideline development was applied which did not require availability of RCTs but used critical appraisal of existing observational literature and group consensus. An international multidisciplinary working group (n = 38) established consensus recommendations in two parts to form the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD). The approach enabled virtual participation worldwide. In Part 1 we developed a standardised approach for assessment and classification of kidney function in patients with cancer using global nephrology standards and working group expertise. Part 2 involved a comprehensive literature search of 59 anticancer drugs followed by a critical appraisal of the evidence certainty through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process and development of dosing recommendations in reduced kidney function. Key external stakeholders (n =9) invited expert contributors (n = 25), and the working group participated in virtual interactive workshops to vote on the acceptability of these recommendations. The participants were provided with evaluation of the literature, and they engaged in several rounds of virtual discussion (involving robustness of the evidence behind recommendations and their real-world application) and anonymous consensus voting. Adapting the ADDIKD guideline development process to a virtual format enabled engagement with a very broad base of specialised international experts especially during the global pandemic. Combining GRADE meth odology with consensus-building approaches was an effective method of producing recommendations (in an area lacking RCTs) by merging critical review of the literature with expert opinion and clinical practice. Copyright (c) 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).