Why do so many drugs fail to get FDA approval?

Some thoughts / notes on the topic of why so many drugs fail to get FDA approval:

• Efficacy-related failures
• Safety-related failures
• assess risk profile 
• ex. systemic toxicity, tumorigenicity, arrhythmias, side effects

• Research, Manufacturing, & Commercial Processes
• optimized for one objective and not the other

• Suboptimal endpoints chosen
• clinical benefit difficult to measure
• disease progression
• overall survivability
• Control Group Problems

• Poorly-chosen Patient Populations
• broad vs. targeted

• Data Management
• Suboptimal data capture / entry
• Investigator bias
• Reporting bias

• Patient Enrollment
• Suboptimal inclusion / exclusion criteria
• Failure to meet enrollment goals
• Cannot recruit enough patients for clinical trial
• Although most patients do not have a problem with the drug; there is a need to redesign the trial
• ex. change the dosage, administration, or procedure
• Lack of money to redesign the trial and start the process over again

• Regulatory
• Key parameters must be clear
• establish criteria needed for safety
• Learning curve for both clinical operations and regulatory agencies
• Agencies fear bad press & litigation
• The framework is still evolving

caco-2 immortalized human epithelial colorectal adenocarcinoma cell line

is used to search for novel compounds to treat colorectal and other cancers