February 26, 2009 Ron Marks, Ph.D. Chief Scientific Officer Clinipace

Is this necessary? www.clinipace.com © 2003-2009 Clinipace, Inc. All Rights Reserved. Pharmaceutical Research and Manufacturers of America, Pharmaceutical Industry Profile 2008 (Washington, DC: PhRMA, March 2008). Regulatory Analysis Operations Design

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

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 3 rd party input early Better manage randomization & monitoring Must consider number of subjects and sites Use “common sense” www.clinipace.com © 2003-2009 Clinipace, Inc. All Rights Reserved. Consider Most data collected is never used…Furthermore, some data are collected excessively or in an inefficient manner. [ Dr. Gwendolyn Fyfe, senior staff scientist ,Genentech] 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

Prioritize your objectives & outcomes

Seek 3 rd 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

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) www.clinipace.com © 2003-2009 Clinipace, Inc. All Rights Reserved. I can tell within 15 minutes of reading a statistical plan if it will succeed. [ Dr. Blair Keagy, UNC School of Medicine]

Number of subjects needed to answer your primary objective

Depends on type & variability of primary outcome

Setting alpha (α) and beta (β)

Listen to the FDA Get to know your review division Work with FDA to determine efficacy and safety criteria Seek guidance early and often www.clinipace.com © 2003-2009 Clinipace, Inc. All Rights Reserved. Red Flags There is no prescribed monitoring frequency. [Robert J. Temple, M.D., Associate Director for Medical Policy, Center for Drug Evaluation and Research, 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

Get to know your review division

Work with FDA to determine efficacy and safety criteria

Seek guidance early and often

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

Don’t over rely on a CRO 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 www.clinipace.com © 2003-2009 Clinipace, Inc. All Rights Reserved. Consider Performance metrics Incentive mix “ Appropriateness” of monitoring plan Relationship with sites

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

Performance metrics

Incentive mix

“ Appropriateness” of monitoring plan

Relationship with sites

Create transparency Manage towards performance metrics Accountability No excuses Maintains study schedule Allows future planning www.clinipace.com © 2003-2009 Clinipace, Inc. All Rights Reserved.

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

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 www.clinipace.com © 2003-2009 Clinipace, Inc. All Rights Reserved. Ron Marks, Ph.D. [email_address]