Specific Populations

Symposium 9: Rethinking Hepatic Impairment Studies: A Patient-centric Approach

Co-Chair & Faculty(s)

• 

  Navin Goyal, PhD

  Senior Director & Group Lead
  Clinical Pharmacology & Pharmacometrics
  Janssen Research & Development, LLC, a Johnson & Johnson Co

  Slides
• MS

  Martina Sahre, PhD

  Policy Lead
  Guidance & Policy
  US Food & Drug Administration

Faculty(s)

• 

  William Smith, MD

  Chief Executive Officer
  Alliance for Multispecialty Research Knoxville
• 

  Xinyuan Zhang, PhD

  Director, Quantitative Clinical Pharmacology
  Daiichi Sankyo Inc

Target Audience:

This Symposium will be important for everyone involved in drug development and prescribing drugs for subjects with hepatic impairment. This includes practicing clinicians (PharmDs and MDs) who treat patients with hepatic impairment and diseases, drug developers (industry) (PharmD, PhD), regulatory agency personnel (PharmD, PhD) and the clinical study sites and investigators.

Description:

Regulatory agencies have published guidance regarding conducting clinical studies to assess the influence of hepatic impairment on the pharmacokinetics (PK) of the investigational drug product to allow generating clinical data to inform the drug label if any dose adjustment may be warranted in this target patient population.

It has become increasingly challenging, if not virtually impossible, to conduct a full PK study design. With the availability of effective HCV treatments, it is getting increasingly difficult to enroll subjects with moderate hepatic impairment. The situation gets worse when seeking subjects with severe impairment. The life expectancy of patients with severe hepatic impairment is approximately 6 to 24 months. Enrolling these subjects exposes them to drugs which provide no benefit but could potentially worsen their condition towards life threatening. Additionally, discussion may be warranted on whether the population of interest may have evolved for example – NASH/NAFLD, hepatitis etc. as opposed to cirrhosis-based Child-Pugh classification.
It's time to rethink an efficient approach that allows generating meaningful data in subjects with varying degrees of hepatic impairment and clearly defining what is a relevant population. Potential approaches to allow generating relevant data to inform dosing recommendations include evaluation of model-based approaches, amending the inclusion/exclusion criteria for Phase 3 clinical studies, considering alternate study designs and evaluating suitability of response-based titration or therapeutic dose monitoring in those with severe impairment. This Symposium will initiate a series of conversations that aim to engage relevant stakeholders to implement a patient-centric approach that benefits the intended target population.

Presentations:

• Hepatic Impairment Studies: Whom Do They Truly Benefit?
  

  Co-Chair & Faculty: Navin S. Goyal, PhD – Janssen Research & Development, LLC, a Johnson & Johnson Co
• Informing Appropriate Dosing in Target Populations
  

  Co-Chair & Faculty: Martina Sahre, PhD – US Food & Drug Administration
• Clinical Research in Subjects With Hepatic Impairment
  

  Faculty: William B. Smith, MD – Alliance for Multispecialty Research Knoxville
• Role of Model-based Approaches in Hepatic Impairment Studies
  

  Faculty: Xinyuan Zhang, PhD – Daiichi Sankyo Inc
• Discussion, Questions & Answers, Learner Feedback & Evaluations