CSRC Blood Pressure Think Tank

Assessment of Pharmacologic-induced Increases in BP

During Clinical Development: Is there a need for more intensive systematic BP evaluation and how should this be considered?

A CSRC Think Tank

Wednesday, July 18, 2012
FDA Headquarters, White Oak, Maryland

7:30am-8:00am

Registration and Continental Breakfast

8:00am-8:15am

Introduction: Philip Sager

8:15am-10:00am   Session I: Drug-induced BP Increases: Clinical Implications (Co-chairs: Norman Stockbridge, Boaz Mendzelevski)

• Lessons Learned from ICH E-14: Norman Stockbridge
• What are the implications of drug-related increases in BP?: 
• Michael Weber
• Preston Dunnmon
• What modifies patient risk associated with a BP increase?: 
• William White
• Alan Charney
• Discussion (50 min) Lead Discussant: Lee Simon

10:00am-10:15am   Break10:15am-12:50pm   Session II: How to Establish Risk Boundaries (Co-chairs: Philip Sager, William White)

• Risk Boundaries: Douglas Throckmorton
• Utility of using Framingham and the Prospective Studies Group databases to estimate risk:
• Potential clinical implications: Peter Kowey
• Christopher O’Donnell
• Worked Example: Raj Madabushi
• Michael Weber
• The optimal approach to using databases to assess risk and the role of the population mean versus the outliers?:
• Jim Neaton
• Tzu-Yun (Z) McDowell
• What is the most important indicator of risk? Mean, AUC, maximal change? Central tendency, categorical changes, and potential PK/PD modeling: Domenic Sica
• Discussion (95 min) Lead Discussant: Robert Temple

12:50pm-1:15pm   Lunch1:15pm-2:00pm   Session III: Preclinical Models (Co-chairs: Peter Kowey, Eric Michelson)

• What are the current animal models and how robust is their sensitivity, specificity, positive and negative predictive values?
• Gary Gintant
• Lorna Ewart
• Discussion (25 min) Lead Discussant: Peter Kowey

2:00pm-3:30pm   Session IV: The Role of Phase I Data and Technical Aspects of BP Measurement During Development (Co-chairs: Jeff Heilbraun, George Mansoor)

• Negative and positive predictive accuracy of Phase 1 data to predict Phase 3 findings in the patient population? Impact of the mechanism of drug-induced BP increases?:
• Milton Pressler
• Jim Keirns
• Discussion (40 min) Lead Discussant: Rick Turner

• What are the required techniques to measure BP and is assay sensitivity required? Is a specific BP study required or can these measurements be incorporated into another study?:
• Jeff Heilbraun
• George Mansoor
• Discussion (35 min) Lead Discussant: Rick Turner

3:30pm-4:00pm4:00pm-5:15pm    Session V: Key Issues (Co-chairs: Robert Blaustein, Michael Weber)

• Targeted BP Assessments: What factors determine the need for a dedicated BP evaluation in humans and the potential role of drug mechanism?: Mary Jane Geiger
• Need for new data: What should be collected in clinical trials to inform future approaches to the clinical significance of drug-induced BP increases?: Jeff Heilbraun
• Major points from the meeting and areas of consensus and disagreement
• William White and Philip Sager
• Discussion (35 min)

Closing Remarks and Next Steps

The CSRC is excited to announce an important Think-Tank on July 18^th that is to be held at the FDA White-Oak Campus.

This Think Tank will bring together industry experts, key regulators, academicians, and core laboratory scientists to explore the potential need for more intensive BP assessment during clinical development, to determine if a new chemical entity increases blood pressure.  The output will be published in a CSRC White Paper. 

Specific topics include:

• Lessons Learned from ICH E-14 that impact the approaches to evaluating the need for more intensive BP assessment during clinical development of non-hypertension medications
• Drug Induced BP increases: Clinical Implications
• Pre-Clinical Models of BP increases and their predictive value
• How to Establish Risk Boundaries for BP increases

• Technical Aspects of BP Measurement during Development
• Targeted BP Assessments