Running A Better Clinical Trial

February 26, 2009

Ron Marks, Ph.D.Chief Scientific Officer

Clinipace

www.clinipace.com© 2003-2009 Clinipace, Inc. All Rights Reserved.

Is this necessary?

Pharmaceutical Research and Manufacturers of America,Pharmaceutical Industry Profile 2008 (Washington, DC: PhRMA, March 2008).

RegulatoryAnalysisOperationsDesign


We already know

Thomson CenterWatch 2003, 2005 survey of sites in U.S.


Take action

• Focus on your circle of influence Design it right Power it right Listen to the FDA Don’t rely too heavily on a CRO Create a transparent study


Be design “intelligent”

• Prioritize your objectives & outcomes

• Seek 3rd party input early• Better manage randomization &

monitoring• Must consider number of

subjects and sites• Use “common sense”

Collect only what’s needed

What are you measuring – time to event vs. survival

Time to document efficacy is usually much shorter than determining safety

GCP allows for “appropriate” monitoring

Random sampling is appropriate for monitoring

ConsiderConsider

Most data collected is never used…Furthermore, some data are collected excessively or in an inefficient manner.[Dr. Gwendolyn Fyfe, senior staff scientist ,Genentech]


Power it right

• Number of subjects needed to answer your primary objective

• Depends on type & variability of primary outcome

• Setting alpha (α) and beta (β)

I can tell within 15 minutes of reading a statistical plan if it will succeed.[Dr. Blair Keagy, UNC School of Medicine]


Listen to the FDA

Objectives are not clear

Outcomes not well-defined or analyzed

Sample size not properly documented

Missing patients without explanation

Un-blinded analytic changes without explanation

SAEs that are dismissed without description as “inter-current illness”

Sloppiness; want most observations to be made by competent person and to be accurate

Red FlagsRed Flags• Get to know your review division

• Work with FDA to determine efficacy and safety criteria

• Seek guidance early and often

There is no prescribed monitoring frequency. [Robert J. Temple, M.D., Associate Director for Medical Policy, Center for Drug Evaluation and Research, FDA]


Don’t over rely on a CRO

Performance metrics

Incentive mix

“Appropriateness” of monitoring plan

Relationship with sites

ConsiderConsider• Balance functional needs vs. complete outsourcing

• Maintain control• You’re the brains, hire for muscle• Expect transparency from your

partners• Demand the use of technology


Create transparency

• Manage towards performance metrics

• Accountability• No excuses• Maintains study

schedule• Allows future planning


Do it now!

• Plan your study thoroughly – think “intelligent design”

• Listen to the FDA• Maintain control of your study• Maintain study schedule through

transparency and comprehensive reporting• Invest in technology-driven processes


Q&A

Ron Marks, [email protected]

Business

Running A Better Clinical Trial