Design, conduct, analysis, and interpretation of clinical studies in patients with impaired kidney function

Chronic kidney disease has been shown to alter the pharmacokinetics of drugs that are eliminated not only via the renal pathway but also by metabolism or nonrenal transport. Guidance documents from regulatory agencies on the pharmacokinetics of drugs in patients with impaired kidney function provide a framework for facilitating study design, conduct, data analysis, and the generation of dosing recommendations. Design considerations include establishment of appropriate enrollment criteria, selection of appropriate matched control group(s), and staging of impaired kidney function by estimated glomerular filtration rate or creatinine clearance. When studies in hemodialysis patients are conducted, optimizing the timing of characterization of the pharmacokinetics profile based on the schedule of hemodialysis sessions will allow for a robust assessment in these patients. In addition to traditional noncompartmental approaches, the use of pharmacometric approaches can integrate data from multiple clinical studies and provide a quantitative rationale for dose selection in patients with impaired kidney function. This article addresses the challenges and opportunities associated with the design, conduct, analysis, and interpretation of clinical studies to allow for their future facilitation and for the establishment of safe and efficacious dosing in patients with impaired kidney function.