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Abstract

As biomarkers have grown in importance throughout the pharma R&D cycle, managers have moved from informal, intuitive ways of dealing with biomarker discovery and implementation to more formal procedures. In all pharmaceutical companies, standard operating procedures (SOPs) for planning, implementing, and employing biomarkers remain a work in progress, continually evolving as still-scarce outcomes data from biomarker-driven programs becomes available.

Based on extensive interviews with senior managers and thought leaders, Biomarker SOPs: Getting Optimum Value from Your Biomarker Programs addresses four primary elements in planning and deploying biomarkers:

• Strategic planning for biomarkers in discovery and development
• Tactical planning for the implementation of biomarkers in R&D programs
• Organizational structures for biomarker implementation
• Approaches to risk/cost-benefit analysis of biomarker programs

For instance, strategic planning for biomarkers attempts to address issues such as whether a clinical measurement will suffice, whether an existing validated biomarker can do the job, or whether a biomarker must be discovered and a method for its measurement must be developed and validated. Although big pharma companies differ in the methods and timing for biomarker strategic planning, they generally start planning very early in the discovery process. In some cases, planning and implementation for efficacy-related biomarkers begin before a final disease target has been determined. Since getting a new biomarker on-line can take a year or more, planning for biomarkers to be used in early development needs to begin as soon as strategic issues can be clarified.

Biomarker SOPs: Getting Optimum Value from Your Biomarker Programs delivers the following value-added insight and analysis into biomarker planning:

• A survey of 33 senior managers involved in biomarker discovery, development, and application at pharmaceutical and biotech companies. The survey reveals in easy-to-scan charts their practices, plans and views about various aspects of biomarker planning and implementation.
• An analysis of 3 basic organizational models for pursuing biomarkers: The Explicit Model, the Implicit Model, and the Hybrid Model. The report illustrates each model with detailed examples from industry.
• The decision process for developing biomarkers in-house or through outsourcing, with examples and case studies from industry.
• A full examination of each element in a tactical biomarker plan, including: the means for biomarker acquisition (if possible), biomarker discovery (if necessary), method development, and biomarker validation. In particular, the report describes the "fit-for-purpose" concept of biomarker validation.
• When biomarker timelines and costs start to mount, some level of business analysis can be beneficial. This can take the form of ROI analysis, cost/risk-vs-benefit analysis, or both. Pfizer is one of the few pharma companies to provide its project teams with a formal software tool for ROI analysis and to encourage its use. This and other biomarker-related efforts under way at Pfizer are presented in a compelling case study of how one big pharma entity is attempting to implement biomarker SOPs.

Biomarkers have moved beyond being used merely to assuage scientific curiosity. They are increasingly being used to answer specific questions that provide critical decision-support data as a compound moves down the pipeline and soaks up more and more R&D dollars. Thus, biomarkers are being used to measure clinical response to a drug, to quantify drug-target interactions, to demonstrate the relevance of a molecule to the pathophysiology of a particular disease, and as safety indicators that can identify subjects who might react adversely to a drug. The rising importance of biomarkers underscores the need for ways to rationally plan for their use. Biomarker SOPs: Getting Optimum Value from Your Biomarker Programs is a must-read for managers charged with making biomarkers pay off for their company.

Table of Contents

Chapter 1. Introduction

• 1.1. Historical Perspective on Biomarkers in Pharma
  • Terminology Recently Evolved
  • A Shift in Emphasis
• 1.2. Current Status of Biomarkers in Pharma
• 1.3. Planning and Implementation Issues
  • Strategic Planning Issues
  • Tactical Planning Issues
  • Organizational Considerations
  • Business Considerations
• 1.4. Precommercial, Collaborative Biomarker Work
  • The Biomarkers Consortium
  • Consortium Projects
  • European Union Consortium
• 1.5. Exploratory Investigational New Drug Applications and the Pipeline Paradigm

Chapter 2 BIOMARKER STRATEGIC PLANNING

Biomarkers Can Serve Multiple Purposes

• 2.1. Planning for Biomarkers
  • Variations among Therapeutic Areas
• 2.2. Biomarkers for Stages along the Pipeline
  • Prediscovery
  • Discovery
  • Early Clinical Development
  • Late-Stage Clinical Development
  • Efficacy Biomarkers
• 2.3. Postmarketing
• 2.4. The Biomarker Strategic Plan

Chapter 3. BIOMARKER IMPLEMENTATION PLANNING

• 3.1. Biomarker Validation
  • Pre-analytical Considerations
  • Method Development
  • Exploratory Method Validation
  • Advanced Method Validation
  • In-Study Validation
• 3.2. Industry Experts' Comments on Biomarker Guidelines, Standard Operating Procedures, and Validation
• 3.3. In-House versus Outsourced Biomarker Identification and Method Development
  • The Biomarkers Consortium
  • Example of Biomarker Implementation

Chapter 4. ORGANIZATIONAL ISSUES

• Translational Medicine
• Centralization vs. Decentralization
• 4.1. Explicit Model
• 4.2. Implicit Model
• 4.3. Hybrid Model

Chapter 5. THE BIOMARKER BUSINESS CASE

• 5.1. Comments on Business Analysis from Industry Experts
  • Cost for One, Benefit for Another

Chapter 6. CASE STUDY IN BIOMARKER PLANNING AND IMPLEMENTATION

• 6.1. Biomarker Typology and Linkage to Outcome: Target, Mechanism, and Outcome Biomarkers
• 6.2. Validation Typology
• 6.3. Stages in the Biomarker Life Cycle: Pathfinding, Research, and Development
• 6.4. Business Considerations: Expense of Development vs. Cost of Wrong Decision
• 6.5. Biomarker Best Practices: Optimize, Maximize, and Balance
• 6.6. Biomarker Validation
• 6.7. Minimally Acceptable Criteria

Chapter 7. RESULTS OF BIOMARKERS SURVEY

• Results and analysis of a Web survey conducted in October 2006

Chapter 8. OBSERVATIONS AND CONCLUSIONS

APPENDIX

• Interviews with Industry Experts
• Ernie Bush, PhD, Director New Initiatives, Cambridge Healthtech Associates
• Claudio Carini, MD, PhD, Vice President, Translational Medicine, Development & Regulatory Services, MDS Pharma Services
• Cynthia Cheesman, Assistant Vice President, Preclinical Project Management, Wyeth
• Nicholas Dracopoli, PhD, Vice President, Clinical Discovery Technologies, Bristol-Myers Squibb
• Darrick Fu, MBA, Associate Vice President for Science and Regulatory Affairs, PhRMA
• Orest Hurko, MD, Assistant Vice President, Translational Research, Wyeth
• David S. Lester, PhD, New York Site Head, Pfizer Human Health Technologies, Global Clinical Technology-Pfizer Global Research and Development
• Terry Lindstrom, PhD, Distinguished Research Fellow; Drug Disposition, Global Pharmacokinetics, and Toxicology, Eli Lilly & Co.
• Bruce H. Littman, MD, Global Head of Translational Medicine, Pfizer
• Michael Stocum, MS, Managing Director, Personalized Medicine Partners
• Stephen A. Williams, MD, PhD, Vice President and Worldwide Head of Clinical Technology, Pfizer

References

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