Clinical Forecasting: A Novel Bayesian Tool for Predicting Phase III Outcomes

Table of Contents

Existing Predictive Tools for Pharmaceutical Forecasting

• Biological Tools
  • Biomarker and Target Discovery via High-Throughput Genomics and Proteomics
  • Bioinformatics: High-Throughput Biomarker and Target Discovery
  • In Silico Drug Discovery with the Connectivity Map
  • Pharmacogenetics and Pharmacogenomics
  • High-Throughput Screens and Animal Models
• Clinical Tools
  • Therapeutic Index
  • Pharmacokinetics
  • Population Pharmacokinetics
  • Pharmacokinetic Models
  • Microdosing
    • Sidebar: Phase IV Postmarketing Surveillance
• Bayesian Market Forecasting and Modeling of Cost-Effectiveness in Drug Development

Description of a Bayesian Clinical Forecasting Model

• Application of a Bayesian Network to Clinical Forecasting in Drug Development
  • Prior Probability of NCE Success and Failure
  • Conditional Probability Tables
  • Training Dataset from Tufts CSDD Sources
  • Independent Dataset Construction
  • Model Evaluation Shows 78% Accurate Prediction of NCE Success on
  • Independent Dataset
• Existing Predictive Tools Empower Bayesian Clinical Forecasting
  • Well-Designed Clinical Forecasting Models Can Boost Accuracy of Market
  • Forecasts
  • Biomarkers and Clinical Predictors Empower Bayesian Forecasting Tools

Case Study: Recombinant Human Activated Protein C, Eli Lilly' s Xigris

• Data Used For Forecast
• Model Predicts Xigris Has Low Probabilities of Clinical Success, Safety and Efficacy

Economic Impact of Bayesian Clinical Forecasting

• Pharmacoeconomic Evaluation
  • Monte Carlo Simulation to Determine Expenditures and Revenues for BN Model and for Pharmaceutical Industry
  • Model Reduced Median Expenditures, Increased Median Cumulative 7-Year Revenues
  • Harnessing the Power of Late-Stage Failure Data and of Industrywide Data Sharing
  • Data Storage Issues: Paper vs. Digital

Societal Impact of Bayesian Clinical Forecasting

• Impact on Children
• Impact on the Elderly

Appendix A

• Brief Overview of Bayesian Networks

Appendix B

Glossary

• Table 1.1. Advantages of Zebrafish in Drug Development
• Table 4.1. Impact of 78% Accurate Clinical Forecasting on Public Companies
• Table 1A. Preference Table for Value Node in Figure 1A

• Figure 1.1. Example of a Pharmacokinetic Profile
• Figure 1.2. Role of Bayesian Networks in Phase IV
• Figure 2.1. Clinical Variables Believed Most Crucial to NCE Clinical Success
• Figure 2.2. Overview of Algorithm for Constructing Leaf Node CPTs
• Figure 2.3. Clinical Forecasting Models Empower Market Forecasts
• Figure 3.1. Prior and Posterior Probability Distributions: Clinical Success for rhAPC
• Figure 3.2. Prior and Posterior Probability Distributions: Safety and Efficacy for rhAPC
• Figure 3.3. Effect of Setting Prior Bias to "Optimistic" on Prior and Posterior Probability Distributions: Clinical Success for rhAPC
• Figure 5.1. Societal Impact of Widespread Adoption of Accurate Clinical Forecasting Methods
• Figure 5.2. Time Lag from Initial NDA Approval to Pediatric sNDA Submission
• Figure 1A. A Simple Influence Diagram (ID)
• Figure 2A. A 3-Layer Bayesian Network