TL11 - Discussion on Study Design and Data Analysis on Pharmacokinetic Studies in Patients with Impaired Renal Function

Abstract: Different drugs are eliminated from the body in various mechanisms which includes renal excretion. It has been shown that impaired renal functions can alter the drug's PK to an extent that a change in dosing regimen is required in many cases. So PK studies in renally impaired population has become an important research topic and integral part of dosing recommendations in labeling. FDA published a draft guidance on how to conduct renal impairment studies (September 2020).
The round table discussion will include:
Question 1: For a full PK study design, FDA recommends inclusion of subjects with kidney failure (eGFR <15 or dialysis patients on non-dialysis days). How will dialysis impact the study design?
Question 2: For the sample size calculation, FDA's example targets a 95% CI within 60% and 140% of the GM (geometric mean) of the PK parameters with at least 80% power. In practice, is there any flexibility for the range of the CI, and 90 vs 95% CI? Is there any practical criteria of different options that is allowed?
Question 3: For the data analysis part, FDA recommends a regression approach where estimated renal function and the PK parameters are treated as continuous variables. For those drug's PK impacted by hemodialysis (HD), should different slopes of eGFR be applied for HD vs other groups in the model where common slope doesn't fit well?

Renal Impairment 

Clinical Trial Design (e.g., Innovative/Complex Design, Estimands, Master Protocol)

ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop 2023